CN113166769A - Methods for altering gene expression of genetic disorders - Google Patents

Methods for altering gene expression of genetic disorders Download PDF

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CN113166769A
CN113166769A CN201980079896.8A CN201980079896A CN113166769A CN 113166769 A CN113166769 A CN 113166769A CN 201980079896 A CN201980079896 A CN 201980079896A CN 113166769 A CN113166769 A CN 113166769A
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transgene
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leu
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N·巴尔茨
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Blue Allele Co ltd
Blueallele Corp
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Abstract

Methods and compositions for modifying the expression of or modifying the coding sequence of an endogenous gene using rare-cutting endonucleases and transposases.

Description

Methods for altering gene expression of genetic disorders
Cross Reference to Related Applications
The present application claims priority from earlier filed and co-pending application USSN 62/754,548 filed on month 1, 2018, USSN 62/755,755 filed on month 5, 2018, USSN 62/756,175 filed on month 6,2018, and USSN 62/799,615 filed on month 31, 2019, the contents of each of which are incorporated herein by reference in their entirety.
Sequence listing
This application contains a sequence listing that has been submitted via EFS-WEB in ASCII format and is hereby incorporated by reference in its entirety. The ASCII copy created on 29/10/2019 was named SEQ _ LISTING _ BA2018-5_ P12988 and was 507,904 bytes in size.
Technical Field
This document is in the field of genome editing and gene therapy. More specifically, this document relates to targeted modification of endogenous genes or reduction of endogenous gene expression as well as gene expression from transgenes.
Background
Monogenic disorders are caused by one or more mutations in a single gene, examples of which include sickle cell disease (the hemoglobin-beta gene), cystic fibrosis (the cystic fibrosis transmembrane conductance regulator), and Tay-Sachs disease (the β -hexosaminidase a gene). Monogenic disorders have been the subject of interest for gene therapy because replacing a defective gene with a functional copy can provide therapeutic benefit. However, one bottleneck for the generation of effective therapies involves the size of the functional copies of the genes. Many delivery methods, including those using viruses, have size limitations that prevent the delivery of large transgenes. Further, many genes have alternative splicing patterns, resulting in a single gene encoding multiple proteins. Methods for correcting regions of defective genes can provide additional means for treating monogenic disorders.
Disclosure of Invention
Gene editing is expected to correct mutations found in genetic disorders, however, creating effective therapies for individual disorders remains a number of challenges, including disorders caused by gain-of-function mutations or disorders requiring precise repair. These challenges are seen in the context of disorders such as spinocerebellar ataxia 2 and parkinson's disease, where the disorders are associated with gain-of-function mutations.
In one aspect, the methods described herein provide novel methods for treating gain-of-function disorders, wherein one or more pathogenic alleles and one or more non-pathogenic alleles are silenced, and anti-silencing coding sequences are used in place of protein expression. The methods can be used to generate genes of one or more isoforms. In one example, rare-cutting endonucleases or transposons can be used to integrate a transgene comprising a silencing sequence and an anti-silencing full or partial coding sequence into an endogenous gene (fig. 12-17). If the transgene includes an anti-silencing partial coding sequence, the transgene may further include a splice acceptor or splice donor operably linked to the partial coding sequence. The transgene may further comprise a promoter operably linked to the anti-silencing coding sequence (if the 5 'region of the gene is targeted) or a terminator operably linked to the anti-silencing coding sequence (if the 3' region of the gene is targeted). The gain-of-function mutation may be a mutation that causes a disease selected from the group consisting of: HD (Huntington's Disease), SBMA (spinal muscular atrophy), SCA1 (vertebral cerebellar Ataxia 1), SCA2 (vertebral cerebellar Ataxia 2), SCA3 (spinocerebellar Ataxia 3 or Machado-Joseph Disease), SCA6 (spinocerebellar Ataxia 6), SCA7 (spinocerebellar Ataxia 7), Fragile X syndrome, Fragile XE mental retardation, Friedrei's Ataxia (Friedrei's Ataxia), myotonic dystrophy type 1, myotonic dystrophy type 2, spinocerebellar Ataxia 8, spinocerebellar Ataxia 12, spinal and bulbar muscular atrophy, JPH3, Amyotrophic Lateral Sclerosis (ALS), hereditary motor and sensory neuro-synephopathies syndrome, PRPS 56, congenital myasthenia gravis 1, congenital lateral sclerosis (ALS), hereditary motor and sensory neuro-synephrosis syndrome, PCS 1, and PCS 3647, Parkinson's disease, tubular sarcoidosis, achondroplasia, lubs X-linked mental retardation syndrome, and autosomal retinitis.
In another aspect, the methods described herein provide novel methods for correcting mutations found at the 5' end of a gene. The methods are based in part on the design of bi-modular bidirectional transgenes compatible with integration through multiple repair pathways. The transgenes described herein may be integrated into the gene by homologous recombination pathways, non-homologous end joining pathways, or both homologous recombination pathways and non-homologous end joining pathways, or by transposition. Further, the integration results in any case (HR, NHEJ forward, NHEJ reverse, transposition forward or transposition reverse) can cause precise correction/alteration of the protein product of the target gene. The transgenes described herein may be used to fix or introduce mutations in the 5' region of a gene of interest. The method is particularly useful where precise editing of a gene or targeted mutant endogenous gene is required that cannot be "replaced" by a synthetic copy due to its size capacity over standard vectors or viral vectors. The methods described herein can be used for application studies (e.g., gene therapy) or basic studies (e.g., creating animal models or understanding gene function).
The methods described herein are compatible with current in vivo delivery vehicles (e.g., adeno-associated viral vectors and lipid nanoparticles), and it addresses several challenges to achieve precise alteration of gene products, particularly those with gain-of-function mutations and those that produce multiple isoforms.
In one embodiment, this document features a method for integrating a transgene into an endogenous gene. The method may comprise delivering a transgene, wherein the transgene carries the first and second splice donor sequences, the first and second coding sequences, and a bi-directional promoter or the first and second promoters (fig. 1). In another aspect, the transgene can also comprise a first terminator and a second terminator. In some embodiments, the first terminator and the second terminator may be replaced by a single bidirectional terminator. The method further comprises administering a rare-cutting endonuclease targeted to a site within the endogenous gene. The result of the method is that the transgene is integrated with the endogenous gene and, regardless of orientation (e.g., forward or reverse), integration will result in precise modification of the amino acid sequence of the protein produced by the endogenous gene (fig. 3 and 4). The methods can comprise the use of any suitable rare-cutting endonuclease, including CRISPR, TAL effector nucleases, zinc finger nucleases, or meganucleases. The rare-cutting endonuclease can target a sequence within an intron or exon of the endogenous gene. The endogenous gene can comprise an ATXN2 gene, and the rare-cutting endonuclease can target intron 1 or exon 1 of the ATXN2 gene. In some embodiments, the CRISPR nuclease can be a CRISPR/Cas12a nuclease or a CRISPR/Cas9 nuclease. In other embodiments, the first coding sequence and the second coding sequence may encode a reporter gene, a purification tag, or an amino acid homologous to the amino acid encoded by the endogenous gene. The first coding sequence and the second coding sequence encode the same amino acid by carrying the same nucleic acid sequence or by carrying different nucleic acid sequences (e.g., using codon degeneracy). The transgene may be synthesized on a viral vector (e.g., an adenoviral vector, an adeno-associated viral vector, or a lentiviral vector). Alternatively, the transgene may be synthesized on a non-viral vector. The above embodiments can result in targeted integration of the transgene in either the forward or reverse direction, while still allowing both products to produce the desired results.
In one embodiment, this document features a method for integrating a transgene into an endogenous gene. The method can comprise delivering a transgene, wherein the transgene carries a first and/or second homology arm, a first and second rare-cutting endonuclease target site, a first and second promoter or a bi-directional promoter, a first and second splice donor sequence, a first and second coding sequence, and optionally a first and second terminator. In some embodiments, the first terminator and the second terminator may be replaced by a single bidirectional terminator. The method further comprises administering a rare-cutting endonuclease that targets a site within the endogenous gene and two sites within the transgene. The result of the method is that the transgene is integrated with the endogenous gene and, regardless of orientation (e.g., forward or reverse), integration will result in precise modification of the amino acid sequence of the protein produced by the endogenous gene. The methods can comprise the use of any suitable rare-cutting endonuclease, including CRISPR, TAL effector nucleases, zinc finger nucleases, or meganucleases. The rare-cutting endonuclease can target a sequence within an intron or exon of the endogenous gene. The endogenous gene can comprise an ATXN2 gene, and the rare-cutting endonuclease can target intron 1 or exon 1 of the ATXN2 gene. In some embodiments, the CRISPR nuclease can be a CRISPR/Cas12a nuclease or a CRISPR/Cas9 nuclease. In other embodiments, the first coding sequence and the second coding sequence may encode a reporter gene, a purification tag, or an amino acid homologous to the amino acid encoded by the endogenous gene. The first coding sequence and the second coding sequence encode the same amino acid by carrying the same nucleic acid sequence or by carrying different nucleic acid sequences (e.g., using codon degeneracy). The transgene may be synthesized on a viral vector (e.g., an adenoviral vector, an adeno-associated viral vector, or a lentiviral vector). Alternatively, the transgene may be synthesized on a non-viral vector. The above embodiments can result in targeted integration of the transgene in either the forward or reverse direction, while still allowing both products to produce the desired results.
In further embodiments, this document features a double-stranded polynucleotide. The double-stranded polynucleotide may comprise a first splice donor sequence and a second splice donor sequence, a first coding sequence and a second coding sequence, a bidirectional promoter, or a first promoter and a second promoter. The double-stranded polynucleotide may further comprise a first and/or second homology arm, a first and second rare-cutting endonuclease target site, and a first and second terminator. In some embodiments, the first terminator and the second terminator may be replaced by a single bidirectional terminator. The coding sequences on the double stranded polynucleotide may be in a reverse complementary orientation. The coding sequences may encode the same amino acid sequence. The coding sequences may comprise the same nucleotide sequence or different nucleic acid sequences (e.g., due to codon degeneracy). The first promoter and the second promoter may be in a reverse complementary orientation to each other.
In another embodiment, this document features a method for integrating a transgene into ATXN 2. The methods can comprise administering a polynucleotide encoding a rare-cutting endonuclease targeted to a site within the ATXN2 gene and a transgene integrated within the ATXN2 gene upon cleavage by the rare-cutting endonuclease. In another example, the rare-cutting endonuclease can be delivered in the form of a protein (e.g., Cas 9or Cas12a protein or TALEN protein) or a ribonucleoprotein complex (e.g., Cas 9or Cas12a and the corresponding gRNA). The transgene may be integrated in a cell comprising an induced pluripotent stem cell, a purkinje cell, a granulosa cell, a neuronal cell, or a glial cell. The transgene integrated within the ATXN2 gene may carry the coding sequence of exon 1 of the ATXN2 gene. The transgene may be integrated within intron 1 or exon 1 of the ATXN2 gene. The transgene may also comprise a promoter upstream of the coding sequence. Any suitable rare-cutting endonuclease (including CRISPR, TAL effector nucleases, zinc finger nucleases or meganucleases) can be used to facilitate integration of the transgene. The transgene may be synthesized on a viral vector (e.g., an adenoviral vector, an adeno-associated viral vector, or a lentiviral vector). Alternatively, the transgene may be synthesized on a non-viral vector.
In another embodiment, this document features a method of modifying expression of an endogenous gene, wherein the method comprises administering a transgene, wherein the transgene comprises a first promoter and a second promoter or a bi-directional promoter, a first nucleic acid sequence that reduces expression of the endogenous gene, and a second nucleic acid sequence that encodes a protein having homology to the protein produced by the endogenous gene. The second nucleic acid sequence may comprise a different nucleic acid sequence (e.g., due to codon degeneracy or lack of sequence) as compared to the first nucleic acid sequence. The transgene described herein can also include a first terminator and a second terminator operably linked to the first nucleic acid sequence and the second nucleic acid sequence. The transgene may be used in cases where at least one allele includes a gain-of-function mutation. The gain-of-function mutation may be a mutation that causes a disease selected from the group consisting of: HD (Huntington's Disease), SBMA (spinal muscular atrophy), SCA1 (vertebral cerebellar Ataxia 1), SCA2 (vertebral cerebellar Ataxia 2), SCA3 (spinocerebellar Ataxia 3 or Machado-Joseph Disease), SCA6 (spinocerebellar Ataxia 6), SCA7 (spinocerebellar Ataxia 7), Fragile X syndrome, Fragile XE mental retardation, Friedrei's Ataxia (Friedrei's Ataxia), myotonic dystrophy type 1, myotonic dystrophy type 2, spinocerebellar Ataxia 8, spinocerebellar Ataxia 12, spinal and bulbar muscular atrophy, JPH3, Amyotrophic Lateral Sclerosis (ALS), hereditary motor and sensory neuro-synephopathies syndrome, PRPS 56, congenital myasthenia gravis 1, congenital lateral sclerosis (ALS), hereditary motor and sensory neuro-synephrosis syndrome, PCS 1, and PCS 3647, Parkinson's disease, tubular sarcoidosis, achondroplasia, lubs X-linked mental retardation syndrome, and autosomal retinitis. The transgene may be carried on a viral vector comprising an adenoviral vector, an adeno-associated viral vector or a lentiviral vector. The transgene may be 4.7kb or less in size. The transgene may be on a non-viral vector. The transgene may be integrated into the genome of the cell.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Although methods and materials similar or equivalent to those described herein can be used in the practice of the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.
The details of one or more embodiments of the invention are set forth in the description below. Other features, objects, and advantages of the invention will be apparent from the description and from the claims.
Drawings
FIG. 1 is a schematic representation of an exemplary transgene for targeted insertion into an endogenous gene and repair of the 5' end. TS1, target site 1; SD1, splice donor site 1; CDS1, coding sequence 1; p1, promoter 1; TS2, target site 2; SD2, splice donor site 2; CDS2, coding sequence 2; p2, promoter 2; HA1, homology arm 1; HA2, homology arm 2; t1, terminator 1; t2, terminator 2; AS1, further sequence 1; AS2, further sequence 2.
Fig. 2 is a diagram showing the integration of a transgene into an intron of an exemplary gene. The transgene includes two target sites for one or more rare-cutting endonucleases, two splice donor sequences, two coding sequences (1.1 and 1.2), and two promoters. Integration is performed by non-homologous end joining (NHEJ). ATG, start codon; TAA, stop codon.
Fig. 3 is a diagram showing transgene integration into an exemplary gene. The transgene comprises two homologous arms, two target sites for one or more rare-cutting endonucleases, two splice donor sequences, two coding sequences (1.1 and 1.2) and two promoters. Integration is performed by Homologous Recombination (HR) or non-homologous end joining (NHEJ).
Fig. 4 is a diagram showing transgene integration into an exemplary gene. The transgene comprises two homologous arms, two target sites for one or more rare-cutting endonucleases, two splice donor sequences, two coding sequences (1.1 and 1.2) and two promoters. Integration is performed by Homologous Recombination (HR) or non-homologous end joining (NHEJ).
FIG. 5 is a schematic representation of the gene products produced upon integration of a transgene described herein. RNA hairpins and dsRNA (top) can be formed if the first and second partial coding sequences within the transgene are homologous to the coding sequence of the endogenous gene. RNA pairing can be reduced if the first and second coding sequences are codon-adjusted, wherein homology to the coding sequence of the endogenous gene is reduced (bottom). T1, transcript 1; t2, transcript 2; t3, transcript 3; +1, RNA synthesis initiation site; s, sense; AntiS, antisense.
FIG. 6 is a schematic representation of exons 1-3 of the ATXN2 gene. The pB1012-D1 and pBA1141 transgenes integrated into the ATXN2 gene are also shown.
FIG. 7 is a graphical representation of the results of integration of the pB1012-D1 or pBA1141 transgene within the ATXN2 gene.
Fig. 8 is a diagram showing transgene integration into exons of an exemplary gene. The transgene comprises two homologous arms, two target sites for one or more rare-cutting endonucleases, two splice donor sequences, two coding sequences (1.1 and 1.2) and two promoters. Integration is performed by Homologous Recombination (HR) or non-homologous end joining (NHEJ).
FIG. 9 is a schematic representation of a transgene comprising a silencing sequence and an anti-silencing coding sequence. Two situations are shown. Case 1 is a diagram depicting a method for silencing both alleles of an endogenous gene while producing a WT protein surrogate. Case 2 is a diagram depicting a method for silencing two alleles (one allele having a gain of function mutation and the other allele having a WT sequence) while generating a protein surrogate. The silencing sequence may be an RNAi cassette. The anti-silent CDS may have a mutation within the silent target sequence to prevent binding. Alternatively, the sequence of the CDS may be removed.
Fig. 10 is a diagram showing the structure of a transgene used to silence the SOD1 allele in a cell, where one allele has a gain-of-function mutation. The transgene also includes codon-adjusted sequences to express the alternative SOD1 protein.
Fig. 11 is a diagram showing an example of a transgene construct for silencing an exemplary endogenous gene and replacing the protein product of the endogenous gene.
Fig. 12 is a diagram showing a general method for silencing gain-of-function alleles while substituting protein production. The gene has integrated into it a partial coding sequence with mutations for preventing silencing by the RNAi cassette. If the integration is at the 5 'or 3' end of the gene, the result may be: results 1, silencing of endogenous genes; result 2, modification of one of the alleles in the endogenous gene; as a result 3, a novel protein is produced from the integration event, wherein the mRNA is resistant to silencing and the protein product comprises the same or different sequence as the original gene.
FIG. 13 is a schematic representation of a transgene used to silence expression of an endogenous gene and replace protein production. CDS1 and CDS2 may be part of the coding sequence of an endogenous gene. The CDS may or may not include mutations at the corresponding targets of the RNAi cassette. The target for integration may be within the intron, but after the endogenous splice donor sequence of the intron. Furthermore, the target for integration may be at the intron-exon junction.
FIG. 14 is a diagrammatic representation of a transgene used to silence expression of an endogenous gene and replace protein production. CDS1 and CDS2 can be the complete coding sequences of endogenous genes. The CDS may or may not include mutations at the corresponding targets of the RNAi cassette. The target for integration may be within the intron, but after the endogenous splice donor sequence of the intron. Furthermore, the target for integration may be at the intron-exon junction.
FIG. 15 is a diagrammatic representation of a transgene used to silence expression of an endogenous gene and replace protein production. CDS1 and CDS2 can be the complete coding sequences of endogenous genes. The CDS may or may not include mutations at the corresponding targets of the RNAi cassette. The target for integration may be within an exon.
FIG. 16 is a diagrammatic representation of a transgene used to silence expression of an endogenous gene and replace protein production. CDS1 and CDS2 can be the complete coding sequences of endogenous genes. The CDS may or may not include mutations at the corresponding targets of the RNAi cassette. The target for integration may be within the 5' UTR. The target for integration may be an intron in the 5' UTR region, but requires a splice acceptor operably linked to the CDS.
FIG. 17 is a diagrammatic representation of a transgene used to silence expression of an endogenous gene and replace protein production. CDS1 and CDS2 may be part of the coding sequence of an endogenous gene. The CDS may or may not include mutations at the corresponding targets of the RNAi cassette. The target for integration may be anywhere between the start codon and the stop codon, but not within the endogenous splice acceptor, or not downstream of the last endogenous splice acceptor.
Fig. 18 is an image of an integrated gel detecting a transgene described herein. The 1, 1kb ladder; 2, pBA 11413' HR junction, expected to be 1594bp in size; 3, pBA 11413' HR junction, expected size 1775 bp; 4, pBA 11413' HR junction, expected size 1775 bp; 5, pBA 11413' NHEJ inverted, expected size 2067 bp; 6, pBA 11423' NHEJ Forward junction, expected to be 813bp in size; 7, pBA 11433' HR junction, expected to be 1225bp in size; 8, pBA 11433' HR junction, expected to be 1407bp in size; 9, pBA 11433' HR junction, expected 1225bp in size; 10, pBA 11433' HR junction, expected to be 1407bp in size; 11, 1kb ladder; 12, control WT DNA with primers oNJB201+ oNJB 190; 13, control WT DNA with primers oNJB202+ oNJB 191; 14, control WT DNA with primers oNJB197+ oNJB 191; 15, control WT DNA with primers oNJB202+ oNJB 211; 16, 1kb ladder; 17, genomic DNA control for pBA1141+ Cas9 transfection; 18, genomic DNA control for pBA1142 transfection; 19, genomic DNA control for pBA1143+ Cas9 transfection; 20, genomic DNA control for pBA1141+ Cas12a transfection; 21, genomic DNA control for pBA1142+ Cas12a transfection; 22, genomic DNA control for pBA1143+ Cas12a transfection; 23, WT control; 24, no DNA control.
Detailed Description
Disclosed herein are methods and compositions for modifying the coding sequence of an endogenous gene. In some embodiments, the method comprises inserting a transgene into an endogenous gene, wherein the transgene provides a partial coding sequence that replaces the coding sequence of the endogenous gene. Also disclosed herein are methods and compositions for reducing endogenous gene expression and expressing surrogate proteins.
In one embodiment, this document features a method of integrating a transgene into an endogenous gene and modifying an mRNA or protein product. The method comprises administering a transgene, wherein the transgene comprises a first splice donor sequence and a second splice donor sequence, a first portion of a coding sequence and a second portion of a coding sequence, a bidirectional promoter or a first promoter and a second promoter, and optionally a first terminator and a second terminator, wherein the transgene is administered with at least one rare-cutting endonuclease that targets a site within the endogenous gene, wherein the transgene is integrated within the endogenous gene. The endogenous gene may be in a eukaryotic cell (including a human cell). The transgene may have a first splice donor operably linked to the first partial coding sequence, and a second splice donor may be operably linked to the second partial coding sequence. Furthermore, the first partial coding sequence may be operably linked to the first promoter and the second partial coding sequence may be operably linked to the second promoter. Alternatively, the first partial coding sequence and the second partial coding sequence may be operably linked to a bidirectional promoter. The transgene having first and second splice donors, first and second partial coding sequences, and first and second promoters may be oriented in a head-to-head orientation. These transgenes can be carried in adeno-associated viral vectors and integrated into the endogenous gene by NHEJ-mediated integration into the targeted double-strand break. The transgene may further include a first target site and a second target site for one or more rare-cutting endonucleases, wherein the target sites are flanking the first splice donor and the second splice donor. Alternatively, the transgene may also include left and right homology arms flanking the first and second splice donors. The transgene may have both a first target site and a second target site for one or more rare-cutting endonucleases, wherein the target sites are flanking the first and second splice donors. The first target site and the second target site may be flanking the first homology arm and the second homology arm. The transgene described in this method may be integrated within an intron or at an exon-intron junction of the endogenous gene. The endogenous gene may be ATXN 2or SNCA, and the integration site may be within an intron or at an exon-intron junction of ATXN2 gene or SNCA gene. When integrated into ATXN2, the transgene may include a first partial coding sequence and a second partial coding sequence encoding a peptide produced by exon 1 of the nonpathogenic ATXN2 gene. When integrated into SNCA, the transgene may include a first portion of coding sequence and a second portion of coding sequence encoding a peptide produced by exon 2 of a non-pathogenic SNCA gene. Integration can occur through the use of CRISPR/Cas12a nuclease or CRISPR/Cas9 nuclease. The first partial coding sequence and the second partial coding sequence may encode the same amino acids. The first coding sequence and the second coding sequence may differ in nucleic acid sequence (e.g., by codon degeneracy), but still encode the same amino acid. The transgene described in this method may be carried on a vector in a form selected from the group consisting of double-stranded linear DNA, double-stranded circular DNA, or a viral vector. The transgene may be carried on a viral vector selected from an adenoviral vector, an adeno-associated viral vector or a lentiviral vector. The transgene may have a total length of equal to or less than 4.7 kb. The method may comprise using a transgene with a partial coding sequence that encodes a peptide produced from a target endogenous gene. The partial coding sequence may be a WT version of the target endogenous gene, and the target endogenous gene may be an aberrant or genetic or a gene that includes a pathogenic mutation. In one embodiment, the host gene is one in which the expression of the protein is aberrant, in other words, is not expressed, is expressed at a lower or higher level than a functional protein, or is expressed such that the protein or a portion thereof is non-functional, thereby causing a disorder in the host. The transgene used in this method may have a first partial coding sequence and a second partial coding sequence that differ in nucleic acid sequence compared to the corresponding endogenous gene. In other words, portions of the coding sequence may be modified (by codon degeneracy) to have minimal homology to the endogenous gene. The method may be used to modify genes associated with gain-of-function disorders, including SOD1, TRPV4, CHRNA1, CHRND, CHRNE, CHRNB1, PRPS1, LRRK2, STIM1, FGFR3, MECP2, SNCA, ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7, TBP, HTT, AR, FXN, DMPK, PABPN1, ATXN8, RHO or C9orf 72.
In another embodiment, this document features a method of integrating a transgene into an endogenous gene and modifying an mRNA or protein product. The method comprises administering a transgene, wherein the transgene comprises left and right transposon ends, first and second splice donor sequences, first and second partial coding sequences, a bidirectional promoter or first and second promoters, and optionally first and second terminators, wherein the transgene is administered with at least one transposase that targets a site within the endogenous gene, wherein the transgene is integrated within the endogenous gene. The endogenous gene may be in a eukaryotic cell (including a human cell). The transgene may have a first splice donor operably linked to the first partial coding sequence, and a second splice donor may be operably linked to the second partial coding sequence. Furthermore, the first partial coding sequence may be operably linked to the first promoter and the second partial coding sequence may be operably linked to the second promoter. Alternatively, the first partial coding sequence and the second partial coding sequence may be operably linked to a bidirectional promoter. The transgene having first and second splice donors, first and second partial coding sequences, and first and second promoters may be oriented in a head-to-head orientation. The transgene may also include left and right transposon ends flanking the first and second splice donors. The transposase can be a CRISPR transposase, wherein the CRISPR transposase comprises a Cas12k or Cas6 protein. These transgenes may be carried within adeno-associated viral vectors. The transgene described in this method may be integrated within an intron or at an exon-intron junction of the endogenous gene. The endogenous gene may be ATXN 2or SNCA, and the integration site may be within an intron or at an exon-intron junction of ATXN2 gene or SNCA gene. When integrated into ATXN2, the transgene may include a first partial coding sequence and a second partial coding sequence encoding a peptide produced by exon 1 of the nonpathogenic ATXN2 gene. When integrated into SNCA, the transgene may include a first portion of coding sequence and a second portion of coding sequence encoding a peptide produced by exon 2 of a non-pathogenic SNCA gene. The first partial coding sequence and the second partial coding sequence may encode the same amino acids. The first coding sequence and the second coding sequence may differ in nucleic acid sequence (e.g., by codon degeneracy), but still encode the same amino acid. The transgene described in this method may be carried on a vector in a form selected from the group consisting of double-stranded linear DNA, double-stranded circular DNA, or a viral vector. The transgene may be carried on a viral vector selected from an adenoviral vector, an adeno-associated viral vector or a lentiviral vector. The transgene may have a total length of equal to or less than 4.7 kb. The method may comprise using a transgene with a partial coding sequence that encodes a peptide produced from a target endogenous gene. The partial coding sequence may be a WT version of the target endogenous gene, and the target endogenous gene may be an aberrant or genetic or a gene that includes a pathogenic mutation. The transgene used in this method may have a first partial coding sequence and a second partial coding sequence that differ in nucleic acid sequence compared to the corresponding endogenous gene. In other words, portions of the coding sequence may be modified (by codon degeneracy) to have minimal homology to the endogenous gene. The method may be used to modify genes associated with gain-of-function disorders, including SOD1, TRPV4, CHRNA1, CHRND, CHRNE, CHRNB1, PRPS1, LRRK2, STIM1, FGFR3, MECP2, SNCA, ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7, TBP, HTT, AR, FXN, DMPK, PABPN1, ATXN8, RHO or C9orf 72.
This document also features a method of integrating a transgene into an endogenous gene and modifying an mRNA or protein product. The method comprises administering a transgene, wherein the transgene comprises a splice acceptor sequence, a partial coding sequence, a terminator, and an RNA interference cassette, wherein the transgene is administered with at least one rare-cutting endonuclease or transposase that targets a site within the endogenous gene, and wherein the transgene is integrated within the endogenous gene. The partial coding sequence may include mutations that prevent silencing by the RNAi cassette. The endogenous gene may be in a eukaryotic cell (including a human cell). The transgene may have a splice acceptor operably linked to a portion of the coding sequence. Furthermore, a partial coding sequence may be operably linked to a terminator. The endogenous gene may be in a eukaryotic cell (including a human cell). The transgene may have a splice acceptor operably linked to a portion of the coding sequence. Furthermore, a partial coding sequence may be operably linked to a terminator. These transgenes can be carried in adeno-associated viral vectors and integrated into the endogenous gene by NHEJ-mediated integration into targeted double strand breaks or by homologous recombination. The transgene may also include a left homology arm and a right homology arm. The transgene described in this method may be integrated within an intron or at an intron-exon junction of the endogenous gene. The RNAi cassette can be a promoter operably linked to a sequence having homology to the endogenous gene. The RNAi cassette can generate shRNA or siRNA. The RNAi cassette can include sequences homologous to the endogenous gene, and portions of the coding sequence within the transgene can include sequences identical to the endogenous gene, however, the target site of the RNAi cassette can be mutated to prevent silencing of expression of the integrated transgene (e.g., with synonymous single nucleotide polymorphisms, insertions, or deletions). Integration can be performed by using CRISPR/Cas12a nuclease or CRISPR/Cas9 nuclease or CRISPR-associated transposase. If a CRISPR-associated transposase is used, the transgene can include a left transposon end and a right transposon end in place of the homology arm. CRISPR-associated transpositions may include Cas6 protein or Cas12k protein. The transgene described in this method may be carried on a vector in a form selected from the group consisting of double-stranded linear DNA, double-stranded circular DNA, or a viral vector. The transgene may be carried on a viral vector selected from an adenoviral vector, an adeno-associated viral vector or a lentiviral vector. The transgene may have a total length of equal to or less than 4.7 kb. The method may comprise using a transgene with a partial coding sequence that encodes a peptide produced from a target endogenous gene. The partial coding sequence may be a WT version of the target endogenous gene, and the target endogenous gene may be an aberrant or genetic or a gene that includes a pathogenic mutation. This method can be used to modify genes associated with gain-of-function disorders, including CACNA1A, ATXN3, SOD1, TRPV4, CHRNA1, CHRND, CHRNE, CHRNB1, PRPS1, LRRK2, STIM1, FGFR3, MECP2, SNCA, ATXN1, ATXN2, CACNA1A, ATXN7, TBP, HTT, AR, FXN, DMPK, PABPN1, ATXN8, RHO, or C9orf 72.
This document also features a method of integrating a transgene into an endogenous gene and modifying an mRNA or protein product. The method comprises administering a transgene, wherein the transgene comprises a splice acceptor sequence, a first portion coding sequence and a second portion coding sequence, a terminator, and an RNA interference cassette, wherein the transgene is administered with at least one rare-cutting endonuclease or transposase that targets a site within the endogenous gene, and wherein the transgene is integrated within the endogenous gene. The first partial coding sequence and the second partial coding sequence may include mutations that prevent silencing by the RNAi cassette. The endogenous gene may be in a eukaryotic cell (including a human cell). The transgene may have a first splice acceptor operably linked to a first portion of the coding sequence and a second splice acceptor operably linked to a second portion of the coding sequence. Furthermore, a first partial coding sequence may be operably linked to a first terminator and a second partial coding sequence may be operably linked to a second terminator. The partial coding sequence may be in a tail-to-tail orientation, with the RNAi cassette in between two terminators. These transgenes can be carried in adeno-associated viral vectors and integrated into the endogenous gene by NHEJ-mediated integration into targeted double strand breaks or by homologous recombination. The transgene may also include a left homology arm and a right homology arm. The transgene described in this method may be integrated within an intron or at an intron-exon junction of the endogenous gene. The RNAi cassette can be a promoter operably linked to a sequence having homology to the endogenous gene. The RNAi cassette can generate shRNA or siRNA. The RNAi cassette can include sequences homologous to the endogenous gene, and portions of the coding sequence within the transgene can include sequences identical to the endogenous gene, however, the target site of the RNAi cassette can be mutated to prevent silencing. Integration can be performed by using CRISPR/Cas12a nuclease or CRISPR/Cas9 nuclease or CRISPR-associated transposase. If a CRISPR-associated transposase is used, the transgene can include a left transposon end and a right transposon end in place of the homology arm. CRISPR-associated transpositions may include Cas6 protein or Cas12k protein. The transgene described in this method may be carried on a vector in a form selected from the group consisting of double-stranded linear DNA, double-stranded circular DNA, or a viral vector. The transgene may be carried on a viral vector selected from an adenoviral vector, an adeno-associated viral vector or a lentiviral vector. The transgene may have a total length of equal to or less than 4.7 kb. The method may comprise using a transgene with a partial coding sequence that encodes a peptide produced from a target endogenous gene. The partial coding sequence may be a WT version of the target endogenous gene, and the target endogenous gene may be an aberrant or genetic or a gene that includes a pathogenic mutation. This method can be used to modify genes associated with gain-of-function disorders, including CACNA1A, ATXN3, SOD1, TRPV4, CHRNA1, CHRND, CHRNE, CHRNB1, PRPS1, LRRK2, STIM1, FGFR3, MECP2, SNCA, ATXN1, ATXN2, CACNA1A, ATXN7, TBP, HTT, AR, FXN, DMPK, PABPN1, ATXN8, RHO, or C9orf 72.
This document also features a method of integrating a transgene into an endogenous gene and modifying an mRNA or protein product. The method comprises administering a transgene, wherein the transgene comprises a splice donor sequence, a partial coding sequence, a promoter, and an RNA interference cassette, wherein the transgene is administered with at least one rare-cutting endonuclease or transposase that targets a site within the endogenous gene, and wherein the transgene is integrated within the endogenous gene. The partial coding sequence may include mutations that prevent silencing by the RNAi cassette. For example, if the RNAi cassette is designed to target sequences within a transcript produced by an endogenous gene, part of the coding sequence (located within the transgene) may include the same coding sequence and corresponding RNAi target as the endogenous gene, thereby subjecting the modified endogenous gene to the same interference caused by the RNAi cassette. To minimize or prevent silencing of the modified endogenous gene, portions of the coding sequence within the transgene may be mutated. The endogenous gene may be in a eukaryotic cell (including a human cell). The transgene may have a splice donor operably linked to a portion of the coding sequence. Furthermore, a partial coding sequence may be operably linked to a promoter. These transgenes can be carried in adeno-associated viral vectors and integrated into the endogenous gene by NHEJ-mediated integration into targeted double strand breaks or by homologous recombination. The transgene may also include a left homology arm and a right homology arm. The transgene described in this method may be integrated within an intron or at an exon-intron junction of the endogenous gene. The RNAi cassette can be a promoter operably linked to a sequence having homology to the endogenous gene. The RNAi cassette can generate shRNA or siRNA. The RNAi cassette can include sequences homologous to the endogenous gene, and portions of the coding sequence within the transgene can include sequences identical to the endogenous gene, however, the target site of the RNAi cassette can be mutated to prevent silencing. The endogenous gene may be ATXN 2or SNCA, and the integration site may be within an intron or at an exon-intron junction of ATXN2 gene or SNCA gene. When integrated into ATXN2, the transgene may include a partial coding sequence encoding a peptide produced by exon 1 of the nonpathogenic ATXN2 gene. The RNAi cassette can be designed to target the transcript sequence of exon 1 of the ATXN2 gene, and the corresponding sequence in the partial coding sequence can be mutated to prevent silencing. When integrated into SNCA, the transgene may include a partial coding sequence encoding a peptide produced by exon 2 of a non-pathogenic SNCA gene. The RNAi cassette can be designed to target the transcript sequence of exon 2 of the SNCA gene, and the corresponding sequence in the partial coding sequence can be mutated to prevent silencing. Integration can be performed by using CRISPR/Cas12a nuclease or CRISPR/Cas9 nuclease or CRISPR-associated transposase. If a CRISPR-associated transposase is used, the transgene can include a left transposon end and a right transposon end in place of the homology arm. CRISPR-associated transpositions may include Cas6 protein or Cas12k protein. The transgene described in this method may be carried on a vector in a form selected from the group consisting of double-stranded linear DNA, double-stranded circular DNA, or a viral vector. The transgene may be carried on a viral vector selected from an adenoviral vector, an adeno-associated viral vector or a lentiviral vector. The transgene may have a total length of equal to or less than 4.7 kb. The method may comprise using a transgene with a partial coding sequence that encodes a peptide produced from a target endogenous gene. The partial coding sequence may be a WT version of the target endogenous gene, and the target endogenous gene may be an aberrant or genetic or a gene that includes a pathogenic mutation. This method can be used to modify genes associated with gain-of-function disorders, including CACNA1A, ATXN3, SOD1, TRPV4, CHRNA1, CHRND, CHRNE, CHRNB1, PRPS1, LRRK2, STIM1, FGFR3, MECP2, SNCA, ATXN1, ATXN2, CACNA1A, ATXN7, TBP, HTT, AR, FXN, DMPK, PABPN1, ATXN8, RHO, or C9orf 72.
This document also features a method of integrating a transgene into an endogenous gene and modifying an mRNA or protein product. The method comprises administering a transgene, wherein the transgene comprises first and second splice donor sequences, first and second partial coding sequences, first and second promoters (or a bi-directional promoter), and an RNA interference cassette, wherein the transgene is administered with at least one rare-cutting endonuclease or transposase that targets a site within the endogenous gene, and wherein the transgene is integrated within the endogenous gene. The partial coding sequence may include mutations that prevent silencing by the RNAi cassette. The endogenous gene may be in a eukaryotic cell (including a human cell). The transgene may have a first splice donor operably linked to a first portion of the coding sequence and a second splice donor operably linked to a second portion of the coding sequence. Furthermore, the first partial coding sequence may be operably linked to the first promoter and the second partial coding sequence may be operably linked to the second promoter. The partial coding sequence can be in a head-adapter orientation, and the RNAi cassette can be placed between the first promoter and the second promoter. These transgenes can be carried in adeno-associated viral vectors and integrated into the endogenous gene by NHEJ-mediated integration into targeted double strand breaks or by homologous recombination. The transgene may also include a left homology arm and a right homology arm. The transgene described in this method may be integrated within an intron or at an exon-intron junction of the endogenous gene. The RNAi cassette can be a promoter operably linked to a sequence having homology to the endogenous gene. The RNAi cassette can generate shRNA or siRNA. The RNAi cassette can include sequences homologous to the endogenous gene, and portions of the coding sequence within the transgene can include sequences identical to the endogenous gene, however, the target site of the RNAi cassette can be mutated to prevent silencing. The endogenous gene may be ATXN 2or SNCA, and the integration site may be within an intron or at an exon-intron junction of ATXN2 gene or SNCA gene. When integrated into ATXN2, the transgene may include a partial coding sequence encoding a peptide produced by exon 1 of the nonpathogenic ATXN2 gene. The RNAi cassette can be designed to target the transcript sequence of exon 1 of the ATXN2 gene, and the corresponding sequence in the partial coding sequence can be mutated to prevent silencing. When integrated into SNCA, the transgene may include a partial coding sequence encoding a peptide produced by exon 2 of a non-pathogenic SNCA gene. The RNAi cassette can be designed to target the transcript sequence of exon 2 of the SNCA gene, and the corresponding sequence in the partial coding sequence can be mutated to prevent silencing. Integration can be performed by using CRISPR/Cas12a nuclease or CRISPR/Cas9 nuclease or CRISPR-associated transposase. If a CRISPR-associated transposase is used, the transgene can include a left transposon end and a right transposon end in place of the homology arm. CRISPR-associated transpositions may include Cas6 protein or Cas12k protein. The transgene described in this method may be carried on a vector in a form selected from the group consisting of double-stranded linear DNA, double-stranded circular DNA, or a viral vector. The transgene may be carried on a viral vector selected from an adenoviral vector, an adeno-associated viral vector or a lentiviral vector. The transgene may have a total length of equal to or less than 4.7 kb. The method may comprise using a transgene with a partial coding sequence that encodes a peptide produced from a target endogenous gene. The partial coding sequence may be a WT version of the target endogenous gene, and the target endogenous gene may be an aberrant or genetic or a gene that includes a pathogenic mutation. The transgene used in this method may have a first partial coding sequence and a second partial coding sequence that differ in nucleic acid sequence compared to the corresponding endogenous gene. In other words, portions of the coding sequence may be modified (by codon degeneracy) to have minimal homology to the endogenous gene. This method can be used to modify genes associated with gain-of-function disorders, including CACNA1A, ATXN3, SOD1, TRPV4, CHRNA1, CHRND, CHRNE, CHRNB1, PRPS1, LRRK2, STIM1, FGFR3, MECP2, SNCA, ATXN1, ATXN2, CACNA1A, ATXN7, TBP, HTT, AR, FXN, DMPK, PABPN1, ATXN8, RHO, or C9orf 72.
The practice of the methods disclosed herein, and the preparation and use of compositions, unless otherwise indicated, employ molecular biology, biochemistry, chromatin structure and analysis, computational chemistry, cell culture, recombinant DNA, and techniques conventional in the art that are within the skill of the art. These techniques are explained fully in the literature. See, e.g., Sambrook et al molecular cloning: a Laboratory Manual (Mobile Laboratory CLONING: arbor Manual), second edition, Cold Spring Harbor Laboratory Press (Cold Spring Harbor Laboratory Press),1989 and third edition, 2001; ausubel et al, MOLECULAR BIOLOGY laboratory Manual (Current Protocols IN MOLECULAR BIOLOGY), John Wiley Giraffe Press (John Wiley & Sons), New York (New York),1987 and periodic updates; "METHODS IN ENZYMOLOGY (METHODS IN Enzyloyloygy)," Academic Press (Academic Press), San Diego (San Diego); wolffe, "CHROMATIN STRUCTURE AND FUNCTION (CHROMATIN STRUCTURE AND FUNCTION"), third edition, academic Press, san Diego, 1998; methods in enzymology, volume 304, "Chromatin" (edited by p.m. wassarman and a.p.wolffe), academic press, san diego, 1999; and METHODS IN MOLECULAR BIOLOGY (METHODS IN MOLECULAR BIOLOGY), Vol 119, "Chromatin Protocols" (edited by Becker, P.B.), Lemana Press (Humana Press), Totorwa (Totowa), 1999.
As used herein, the terms "nucleic acid" and "polynucleotide" are used interchangeably. Nucleic acids and polynucleotides may refer to deoxyribonucleotide or ribonucleotide polymers in either linear or circular configuration and in either single-or double-stranded form. These terms should not be construed as limiting the length of the polymer. The term may encompass natural nucleotides as well as known analogs of nucleotides that are modified in the base, sugar, and/or phosphate moieties.
The terms "polypeptide", "peptide" and "protein" are used interchangeably to refer to amino acid residues that are covalently linked together. The terms also apply to proteins in which one or more amino acids are chemical analogs or modified derivatives of the corresponding naturally occurring amino acid.
The terms "operatively connected" or "operatively connected" are used interchangeably and refer to the juxtaposition of two or more components (e.g., sequence elements) arranged such that both components function properly and such that at least one of the components is capable of mediating a function imposed on at least one other component. For example, a transcriptional regulatory sequence, such as a promoter, is operably linked to a coding sequence if it controls the level of transcription of the coding sequence in response to the presence or absence of one or more transcriptional regulatory factors. Transcriptional regulatory sequences are typically operably linked to a coding sequence in cis, but need not be directly adjacent thereto. For example, enhancers are transcriptional regulatory sequences operably linked to a coding sequence, even if they are not contiguous.
As used herein, the term "cleavage" refers to the breaking of the covalent backbone of a nucleic acid molecule. Cleavage can be initiated by a variety of methods, including but not limited to enzymatic or chemical hydrolysis of the phosphodiester bond. Cleavage may refer to single-stranded nicks and double-stranded breaks. Double-strand breaks may be due to two different single-strand nicks. Nucleic acid cleavage can result in the generation of blunt ends or staggered ends. In certain embodiments, rare-cutting endonucleases are used for targeted double-stranded or single-stranded DNA cleavage.
An "exogenous" molecule may refer to a small molecule (e.g., a sugar, lipid, amino acid, fatty acid, phenolic compound, alkaloid) or a large molecule (e.g., a protein, nucleic acid, carbohydrate, lipid, glycoprotein, lipoprotein, polysaccharide) that is produced or present extracellularly or not normally present in a cell, or any modified derivative of the above or any complex that includes one or more of the above molecules. Exogenous molecules can be introduced into the cell. Methods for introducing foreign molecules into cells may include lipid-mediated transfer, electroporation, direct injection, cell fusion, particle bombardment, calcium phosphate co-precipitation, DEAE-dextran-mediated transfer, and viral vector-mediated transfer.
An "endogenous" molecule is a small molecule or a large molecule that is present in a particular cell at a particular developmental stage under particular environmental conditions. The endogenous molecule can be a nucleic acid, a chromosome, the genome of a mitochondrion, a chloroplast or other organelle, or a naturally occurring episomal nucleic acid. Additional endogenous molecules may comprise proteins, such as transcription factors and enzymes.
As used herein, "gene" refers to a region of DNA encoding a gene product, including all regions of DNA that regulate the production of the gene product. Thus, genes include, but are not necessarily limited to: promoter sequences, terminators, translation control sequences such as ribosome binding sites and internal ribosome entry sites, enhancers, silencers, insulators, border elements, origins of replication, matrix attachment sites, and locus control regions.
"endogenous gene" refers to a region of DNA that is normally present in a particular cell that encodes a gene product, as well as all regions of DNA that regulate the production of the gene product.
"Gene expression" refers to the conversion of information contained in a gene into a gene product. The gene product may be the direct transcription product of a gene. For example, the gene product can be, but is not limited to, an mRNA, tRNA, rRNA, antisense RNA, ribozyme, structural RNA, or a protein produced by translation of an mRNA. Gene products also include RNA modified by processes such as capping, polyadenylation, methylation and editing, as well as proteins modified by, for example, methylation, acetylation, phosphorylation, ubiquitination, ADP-ribosylation, myristylation and glycosylation.
"encoding" refers to the conversion of information contained in a nucleic acid into a product, wherein the product can be produced from the direct transcription product of the nucleic acid sequence. For example, the product can be, but is not limited to, an mRNA, tRNA, rRNA, antisense RNA, ribozyme, structural RNA, or protein produced by translation of an mRNA. Gene products also include RNA modified by processes such as capping, polyadenylation, methylation and editing, as well as proteins modified by, for example, methylation, acetylation, phosphorylation, ubiquitination, ADP-ribosylation, myristylation and glycosylation.
A "target site" or "target sequence" is a nucleic acid sequence to which a binding molecule will bind, provided that sufficient binding conditions are present, such as an endonuclease or a transposase, comprising, for example, a rare-cutting endonuclease or a CRISPR-associated transposase. The target site may be an endogenous gene native to the cell or may be heterologous.
As used herein, the term "recombination" refers to the process of genetic information exchange between two polynucleotides. The term "Homologous Recombination (HR)" refers to a particular form of recombination that can occur, for example, during repair of a double-strand break. Homologous recombination requires the presence of nucleotide sequence homology on the "donor" molecule. The donor molecule can be used by the cell as a template for repairing double strand breaks. Information within the donor molecule that differs from the genomic sequence at or near the double strand break can be stably incorporated into the genomic DNA of the cell.
As used herein, the term "homologous" refers to a nucleic acid or amino acid sequence having similarity to a second sequence of nucleic acids or amino acids. In some embodiments, homologous sequences can have at least 80% sequence identity to each other (e.g., 81%, 85%, 90%, 95%, 96%, 97%, 98%, or 99% sequence identity).
A "target site" or "target sequence" defines a portion of a nucleic acid to which a rare-cutting endonuclease or CRISPR-associated transposase will bind, provided that sufficient binding conditions are present.
As used herein, the term "transgene" refers to a nucleic acid sequence that can be transferred to an organism or cell. A transgene may include a gene or nucleic acid sequence not normally found in the target organism or cell. In addition, a transgene may include copies of a gene or nucleic acid sequence that are typically present in the target organism or cell. The transgene may be an exogenous DNA sequence introduced into the cytoplasm or nucleus of the target cell. In one embodiment, a transgene described herein contains a partial coding sequence, wherein the partial coding sequence encodes a portion of a protein produced by a gene in a host cell.
As used herein, the term "pathogenic" refers to anything that can cause disease. Pathogenic mutations may refer to modifications in the gene causing the disease. Pathogenic genes are meant to include modified genes that cause disease. For example, the pathogenic ATXN2 gene of a patient with spinocerebellar ataxia 2 refers to the ATXN2 gene with an extended CAG trinucleotide repeat, wherein the extended CAG trinucleotide repeat causes the disease.
As used herein, the term "tail-to-tail" refers to the orientation of two units in opposite and opposite directions. The two units may be two sequences on a single nucleic acid molecule, wherein the 3' ends of each sequence are placed adjacent to each other. For example, a first nucleic acid having the elements [ splice acceptor 1] - [ partial coding sequence 1] - [ terminator 1] and a second nucleic acid having the elements [ splice acceptor 2] - [ partial coding sequence 2] - [ terminator 2] in the 5 'to 3' orientation can be placed in a tail-to-tail orientation to produce [ splice acceptor 1] - [ partial coding sequence 1] - [ terminator 2RC ] - [ partial coding sequence 2RC ] - [ splice acceptor 2RC ], where RC refers to the reverse complement.
As used herein, the term "head joint" refers to the orientation of two units in opposite and opposite directions. The two units may be two sequences on a single nucleic acid molecule, wherein the 5' ends of each sequence are placed adjacent to each other. For example, a first nucleic acid having the elements [ promoter 1] - [ partial coding sequence 1] - [ splice donor 1] and a second nucleic acid having the elements [ promoter 2] - [ partial coding sequence 2] - [ splice donor 2] in the 5 'to 3' orientation can be placed in a head-to-head orientation to produce [ splice donor 1Rc ] - [ partial coding sequence 1Rc ] - [ promoter 2] - [ partial coding sequence 2] - [ splice donor 2], wherein Rc refers to the reverse complement.
As used herein, the term "integration" refers to the process of adding DNA to a target region of DNA. Integration can be facilitated by several different means, including non-homologous end joining, homologous recombination, or targeted transposition, as described herein. For example, integration of a user-provided DNA molecule into a target gene may be facilitated by non-homologous end joining. Here, a targeted double strand break is made within the target gene and a user-supplied DNA molecule is administered. The user-supplied DNA molecule may include exposed DNA ends to facilitate capture during target gene repair via non-homologous end joining. The exposed ends can be present on the DNA molecule after administration (i.e., administration of a linear DNA molecule) or generated after administration to the cell (i.e., the rare-cutting endonuclease cleaves the user-provided DNA molecule intracellularly to expose the ends). In addition, the user-supplied DNA molecule may be carried on a viral vector (including adeno-associated viral vectors). In another example, integration occurs by homologous recombination. Here, the user-supplied DNA may carry left and right homology arms. In another example, integration occurs by transposition. Here, the DNA provided by the user carries the left and right ends of the transposon.
The term "intron-exon junction" refers to a specific location within a gene. The specific position is between the last nucleotide in an intron and the first nucleotide of a subsequent exon. When a transgene described herein is integrated, the transgene may be integrated within an "intron-exon junction". If the transgene comprises a cargo, the cargo will be integrated at a position immediately after the last nucleotide in the intron. In some cases, integration of a transgene within an intron-exon junction may result in removal of sequences within the exon (e.g., by HR integration and replacement of sequences within the exon with a cargo within the transgene).
The term "exon-intron junction" refers to a specific location within a gene. The specific position is between the last nucleotide in an exon and the first nucleotide of a subsequent intron. When a transgene described herein is integrated, the transgene may be integrated within an "exon-intron junction. If the transgene comprises a cargo, the cargo will be integrated at a position immediately preceding the first nucleotide in the intron. In some cases, integration of a transgene within an exon-intron junction can result in removal of the sequence within the exon (e.g., by HR integration and replacement of the sequence within the exon with a cargo within the transgene).
As used herein, the term "partial coding sequence" refers to a nucleic acid sequence that encodes a partial protein. A partial coding sequence may encode a protein that includes one or fewer amino acids as compared to the wild-type protein or functional protein. The partial coding sequence may encode a partial protein having homology to the wild-type protein or a functional protein. The term "partial coding sequence" when referring to a "partial coding sequence" operably linked to a promoter refers to a nucleotide sequence that encodes the N-terminus of a protein of interest. For example, a portion of the coding sequence of the ATXN2 gene that includes 25 exons can include nucleotides that encode peptides produced by exons 1, 1-2, 1-3, 1-4, 1-5, 1-6, 1-7, 1-8, 1-9, 1-10, 1-11, 1-12, 1-13, 1-14, 1-15, 1-16, 1-17, 1-18, 1-19, 1-20, 1-21, 1-22, 1-23, or 1-24. The term "partial coding sequence" when referring to a "partial coding sequence" operably linked to a terminator refers to a nucleotide sequence encoding the C-terminus of a protein of interest. For example, a portion of the coding sequence of the ATXN2 gene may comprise nucleotides encoding a peptide produced by exons 2-25, 3-25, 4-25, 5-25, 6-25, 7-25, 8-25, 9-25, 10-25, 11-25, 12-25, 13-25, 14-25, 15-25, 16-25, 17-25, 18-25, 19-25, 20-25, 21-25, 22-25, 23-25, 24-25, or 25.
The term "anti-silencing coding sequence" or "anti-silencing moiety coding sequence" refers to a nucleic acid sequence that, when used as a template to produce an RNA, is not or is not likely to be silenced by a corresponding RNAi molecule. This may be due to a mutation within the RNAi target site or a deletion of said site.
The methods and compositions described in this document can use a transgene with a cargo sequence. The term "cargo" may refer to elements such as the complete or partial coding sequence of a gene, partial sequences of a gene carrying a single nucleotide polymorphism relative to the WT or altered target, splice acceptors, splice donors, promoters, terminators, transcriptional regulatory elements, RNAi cassettes, purification tags (e.g., glutathione-S-transferase, poly (His), maltose-binding protein, Strep-tag, Myc-tag, AviTag, HA-tag, or chitin-binding protein), or reporter genes (e.g., GFP, RFP, lacZ, cat, luciferase, puro, neomycin). As defined herein, a "cargo" may refer to a sequence integrated at a target site within a transgene. For example, a "cargo" can refer to sequences on the transgene between two homology arms, two rare-cutting endonuclease target sites, or the left and right transposon ends.
The term "homologous sequence" refers to a nucleic acid sequence having homology to a second nucleic acid. For example, a homologous sequence may be present on a donor molecule as an "arm with homology" or "homology arm". The homology arm may be a nucleic acid sequence within the donor molecule that facilitates homologous recombination with a second nucleic acid. In one embodiment, the homologous sequence or homology arm has homology to an endogenous gene. As defined herein, a homology arm may also be referred to as an "arm". In donor molecules with two homology arms, the homology arms can be referred to as "arm 1" and "arm 2". In one aspect, the cargo sequence may be flanked by a first homology arm and a second homology arm.
The term "bidirectional terminator" refers to a terminator that can terminate transcription of an RNA polymerase in either the sense or antisense orientation. The bidirectional terminator may comprise a non-chimeric sequence of DNA as compared to two unidirectional terminators in a tail-to-tail orientation. Examples of bidirectional terminators include ARO4, TRP1, TRP4, ADH1, CYC1, GAL1, GAL7, and GAL10 terminators.
The term "bidirectional promoter" refers to a promoter that can initiate transcription of an RNA polymerase in either sense or antisense orientation. A bi-directional promoter may include a non-chimeric sequence of DNA as compared to two unidirectional promoters in a head-to-head orientation. Examples of bi-directional promoters include those described in Trinklein et al, genomics research (Genome Res.) 14:62-66,2004, the entire disclosure of which is incorporated herein by reference, except for any definitions, disclaimers, negatives, and inconsistencies.
The 5 'or 3' end of a nucleic acid molecule refers to the orientation and chemical orientation of the nucleic acid. As defined herein, the "5' end of a gene" may include an exon having a start codon, but not an exon having a stop codon. As defined herein, the "3' end of a gene" may include an exon having a stop codon, but not an exon having a start codon.
The term "RNAi" refers to RNA interference, a process that uses RNA molecules to inhibit or reduce gene expression or translation. RNAi can be induced by using small interfering RNA (siRNA) or short hairpin RNA (shRNA).
The term "ATXN 2" gene refers to the gene encoding the enzyme spinocerebellar ataxia-2. Representative sequences of the ATXN2 gene can be found in the NCBI reference sequence: NG _011572.3 and the corresponding SEQ ID NO: 56. Exon and intron boundaries can be defined by the sequences provided in SEQ ID No. 56. In particular, exon 1 comprises the sequence from 282 to 532. Exon 2 contains the sequence from 43397 to 43433. Exon 3 comprises the sequence from 45099 to 45158. Exon 4 comprises the sequence from 46339 to 46410. Exon 5 comprises the sequence from 46886 to 47036. Exon 6 comprises the sequence from 74000 to 74124. Exon 7 comprises the sequence from 78343 to 78434. Exon 8 comprises the sequence from 79240 to 79437. Exon 9 contains the sequence from 80889 to 81067. Exon 10 comprises the sequence from 82953 to 83162. Exon 11 comprises the sequence from 85777 to 85959. Exon 12 comprises the sequence from 88734 to 88931. Exon 13 comprises the sequence from 89318 to 89425. Exon 14 comprises the sequence from 89697 to 89767. Exon 15 comprises the sequence from 110536 to 110840. Exon 16 comprises the sequence from 112492 to 112555. Exon 17 comprises the sequence from 113451 to 113603. Exon 18 comprises the sequence from 113985 to 114051. Exon 19 comprises the sequence from 128574 to 128758. Exon 20 comprises the sequence from 129076 to 129208. Exon 21 comprises the sequence from 134601 to 134654. Exon 22 comprises the sequence from 141957 to 142102. Exon 23 comprises the sequence from 143060 to 143287. Exon 24 comprises the sequence from 145471 to 145639. Exon 25 comprises the sequence from 146476 to 146504. Intron 1 comprises a sequence from 533 to 43396. Intron 2 comprises a sequence from 43434 to 45098. Intron 3 comprises a sequence from 45159 to 46338. Intron 4 comprises the sequence from 46411 to 46885. Intron 5 comprises the sequence from 47037 to 73999. Intron 6 comprises the sequence from 74125 to 78342. Intron 7 comprises the sequence from 78435 to 79239. Intron 8 comprises the sequence 79438 through 80888. Intron 9 contains the sequence 81068-82952. Intron 10 comprises a sequence from 83163 to 85776. Intron 11 comprises the sequence from 85960 to 88733. Intron 12 comprises the sequence 88932 through 89317. Intron 13 comprises the sequence from 89426 to 89696. Intron 14 comprises a sequence from 89768 to 110535. Intron 15 comprises a sequence from 110841 to 112491. Intron 16 comprises a sequence from 112556 to 113450. Intron 17 comprises the sequence from 113604 to 113984. Intron 18 comprises a sequence from 114052 to 128573. Intron 19 comprises the sequence from 128759 to 129075. Intron 20 comprises the sequence from 129209 to 134600. Intron 21 comprises the sequence from 134655 to 141956. Intron 22 comprises a sequence from 142103 to 143059. Intron 23 comprises the sequence from 143288 to 145470. Intron 24 comprises a sequence from 145640 to 146475. An example of a pathogenic mutation in ATXN2 comprises a CAG trinucleotide extension (32 or more CAG repeats) in exon 1. Examples of non-pathogenic mutations include ClinVar accession numbers VCV000522367, VCV000522368, VCV000522369, VCV000522370, VCV000128509, VCV000128508, VCV000128507, VCV 000218618.
The term "SNCA" gene refers to a gene encoding the protein synuclein alpha. Representative sequences of SNCA genes can be found in the NCBI reference sequence: NG _011851.1 and the corresponding SEQ ID NO: 55. The exon and intron boundaries can be defined by the sequences provided in SEQ ID NO: 55. In particular, exon 1 comprises a sequence from 1 to 200. Exon 2 contains the sequence from 1470 to 1615. Exon 3 contains the sequence from 8978 to 9019. Exon 4 contains the sequence from 14774 to 14916. Exon 5 comprises the sequence from 107885 to 107968. Exon 6 contains the sequence from 110502 to 113063. Intron 1 comprises a sequence from 201 to 1469. Intron 2 comprises the sequence from 1616 to 8977. Intron 3 comprises the sequence 9020 to 14773. Intron 4 comprises the sequence from 14917 to 107884. Intron 5 comprises the sequence from 107969 to 110501. The start codon is present in intron 2. Examples of pathogenic mutations in SNCA include repeats or triplicates of genes a53T, G51D, E46K, and a 30P. Examples of non-pathogenic mutations include ClinVar accession numbers VCV000350063, VCV000350064, VCV000350086, and VCV 000350093.
As defined herein, the SOD1 gene refers to a gene that produces the enzyme superoxide dismutase. Representative sequences of the SOD1 gene can be found in the NCBI reference sequence: NG _008689.1 and the corresponding SEQ ID NO: 57. The exon and intron boundaries can be defined by the sequences provided in SEQ ID NO: 57. Specifically, exon 1 comprises the sequence from 5001 to 5220. Exon 2 contains the sequence from 9169 to 9265. Exon 3 comprises the sequence from 11828 to 11897. Exon 4 comprises the sequence from 12637 to 12754. Exon 5 contains the sequence 13850 to 14310. Intron 1 comprises a sequence from 5221 to 9168. Intron 2 comprises the sequence from 9170 to 11827. Intron 3 comprises the sequence 11898 through 12636. Intron 4 comprises the sequence from 12755 to 12849. The methods described herein provide a transgene for integration into the SOD1 gene. The transgene may include a promoter, a partial SOD1 coding sequence, and a splice donor, and the integration site may be within intron 1,2, 3, or 4 of the endogenous SOD1 gene. Further, the transgene may include an RNAi cassette targeting the endogenous SOD1 transcript, a promoter, a partial SOD1 coding sequence (resistant to silencing by the RNAi cassette), and a splice donor. The transgene may be integrated in intron 1,2, 3 or 4 of the endogenous SOD1 gene. Furthermore, the transgene may include a splice acceptor, a partial SOD1 coding sequence (resistant to silencing by the RNAi cassette), a terminator, and an RNAi cassette targeted to the endogenous SOD1 transcript. The transgene may be integrated in intron 1,2, 3 or 4 of the endogenous SOD1 gene. Examples of pathogenic mutations in SOD1 include A5V, C7F, G13R, G17S, E22K, G38R, L39V, G42S, F46C, H47R, G73S, H81R, L85V, G86R, G94R, E101G, I105F and L107V. Examples of non-pathogenic mutations include ClinVar accession numbers VCV000440292, VCV000256202, VCV000586633 and VCV 000395173.
As defined herein, RHO gene refers to a gene that produces the protein rhodopsin. Representative sequences of the RHO gene can be found in the NCBI reference sequence: NC-000003.12 and the corresponding SEQ ID NO: 58. Exon and intron boundaries can be defined by the sequences provided in SEQ ID NO: 58. In particular, exon 1 comprises a sequence from 1 to 456. Exon 2 contains the sequence from 2238 to 2406. Exon 3 contains the sequence from 3613 to 3778. Exon 4 comprises the sequence 3895 to 4134. Exon 5 comprises the sequence from 4970 to 6706. Intron 1 comprises the sequence from 457 to 2237. Intron 2 comprises the sequence from 2407 to 3612. Intron 3 comprises a sequence from 3779 to 3894. Intron 4 comprises a sequence from 4135 to 4969. The methods described herein provide transgenes for integration into the RHO gene. The transgene may include a promoter, a partial RHO coding sequence and a splice donor, and the integration site may be within intron 1,2, 3 or 4 of the endogenous RHO gene. Further, the transgene may include an RNAi cassette targeting the endogenous RHO transcript, a promoter, a partial RHO coding sequence (resistant to silencing by the RNAi cassette), and a splice donor. The transgene may be integrated in intron 1,2, 3 or 4 of the endogenous RHO gene. Furthermore, the transgene may include a splice acceptor, a partial RHO coding sequence (resistant to silencing by the RNAi cassette), a terminator, and an RNAi cassette targeting the endogenous RHO transcript. The transgene may be integrated in intron 1,2, 3 or 4 of the endogenous RHO gene. Examples of pathogenic mutations in the RHO include ciinvar accession numbers VCV000013039, VCV000013031, VCV000013017, VCV000013042, VCV000013018, VCV000625297, VCV000013055, VCV000013013, VCV000013019, VCV000013047, VCV000013016, VCV000013020, VCV000013021, VCV000013045, VCV000013054, VCV000625301, VCV000013038, VCV000013022, VCV000013035, VCV000013048, VCV 0003730303030303013094, VCV000013028, VCV000279882, VCV000013024, VCV000013046, VCV 000029130875, VCV 000000013049, VCV000417867, VCV000013050, VCV 143080, 0000130080, 000013031, VCV 00013031, VCV000013031, VCV000013023, VCV 00013031, VCV000013031, VCV000013023, VCV000013031, VCV000013032, VCV000013031, VCV000013023, VCV000013031, VCV000013023, VCV000013031, VCV000013023, VCV000013031, VCV000013031, 000013032, VCV000013031, VCV 0000v, VCV000013031, VCV000013023, VCV, and 000013031, 000013031 v, VCV000013031, VCV, 0000v, VCV000013031, VCV000013023, VCV000013031 v, VCV 0000v, VCV, 000013023, VCV, 000013031 v, VCV, 000013031, VCV000013023, VCV, 000013032, VCV000013031 v, VCV000013032, VCV000013031 v, VCV, and 000013031 v, VCV000013032, VCV, and 000013031 v, VCV. Examples of non-pathogenic mutations include ClinVar accession numbers VCV000343272, VCV000256383, VCV000281512, VCV000256384, VCV000256382, VCV000343286, VCV000343290, VCV000343302, VCV000343303, VCV000343306 and VCV 000606153.
As defined herein, the C9orf72 gene refers to a gene that produces proteins in various tissues and is associated with amyotrophic lateral sclerosis. Representative sequences of the C9orf72 gene can be found in the NCBI reference sequence: NG _031977.1 and the corresponding SEQ ID NO: 59. Exon and intron boundaries can be defined by the sequences provided in SEQ ID No. 59. In particular, exon 1 comprises a sequence from 1 to 158. Exon 2 contains the sequence from 6703 to 7190. Exon 3 comprises the sequence from 8277 to 8336. Exon 4 comprises the sequence from 11391 to 11486. Exon 5 comprises the sequence from 12218 to 12282. Exon 6 comprises the sequence from 13568 to 13640. Exon 7 comprises the sequence from 15260 to 15376. Exon 8 contains the sequence from 17071 to 17306. Exon 9 contains the sequence from 23160 to 23217. Exon 10 comprises the sequence from 25201 to 25310. Exon 11 comprises the sequence from 25445 to 27321. Intron 1 comprises a sequence from 159 to 6702. Intron 2 comprises the sequence 7191 through 8276. Intron 3 comprises the sequence 8337 to 11390. Intron 4 comprises the sequence from 11487 to 12217. Intron 5 comprises the sequence 12283 through 13567. Intron 6 comprises the sequence from 13641 to 15259. Intron 7 contains the sequence from 15377 to 17070. Intron 8 contains the sequence from 17307 to 23159. Intron 9 comprises the sequence from 23218 to 25200. Intron 10 comprises a sequence from 25311 to 25444. The methods described herein provide a transgene for integration into the C9orf72 gene. The transgene may include a promoter, a portion of the C9orf72 coding sequence, and a splice donor, and the integration site may be within intron 1,2, 3, 4,5, 6, 7, 8, 9, or 10 of the endogenous C9orf72 gene. Further, the transgene may include an RNAi cassette targeting the endogenous C9orf72 transcript, a promoter, a partial C9orf72 coding sequence (resistant to silencing by the RNAi cassette), and a splice donor. The transgene may be integrated within intron 1,2, 3, 4,5, 6, 7, 8, 9, or 10 of the endogenous C9orf72 gene. Furthermore, the transgene may include a splice acceptor, a portion of the C9orf72 coding sequence (resistant to silencing by the RNAi cassette), a terminator, and an RNAi cassette that targets the endogenous C9orf72 transcript. The transgene may be integrated within intron 1,2, 3, 4,5, 6, 7, 8, 9, or 10 of the endogenous C9orf72 gene. Examples of pathogenic mutations in C9orf72 include repeats, triple or quadruple repeats of the C9or72 gene or an extension of the GGGGCC repeat sequence. Examples of non-pathogenic mutations include ClinVar accession numbers VCV000366486, VCV000366521, VCV000366524, VCV000183033 and VCV 000611705.
As defined herein, the CHRNA1 gene refers to a gene that produces the nicotinic α 1 subunit of the cholinergic receptor protein. Representative sequences of the CHRNA1 gene can be found in the NCBI reference sequence: NG _ 008172.1. As defined herein, the CHRND gene refers to a gene that produces the nicotinic delta subunit of the cholinergic receptor protein. Representative sequences of the CHRND gene can be found in the NCBI reference sequence: NG _ 008028.1. As defined herein, CHRNE gene refers to a gene that produces the nicotinic epsilon subunit of the cholinergic receptor protein. Representative sequences of the CHRNE gene can be found in the NCBI reference sequence: NG _ 008029.2. As defined herein, the CHRNB1 gene refers to a gene that produces the nicotinic β 1 subunit of the cholinergic receptor protein. Representative sequences of the CHRNB1 gene can be found in the NCBI reference sequence: NG _ 008026.1. As defined herein, the PRPS1 gene refers to a gene that produces the protein phosphoribosyl-pyrophosphate synthetase 1. Representative sequences of the PRPS1 gene can be found in the NCBI reference sequence: NG _ 008407.1. As defined herein, the LRRK2 gene refers to a gene that produces protein leucine-rich repeat kinase 2. Representative sequences of the LRRK2 gene can be found in the NCBI reference sequence: NG _ 011709.1. As defined herein, the STIM1 gene refers to the gene that produces protein matrix interacting molecule 1. Representative sequences of the STIM1 gene can be found in the NCBI reference sequence: NG _ 016277.1. As defined herein, the FGFR3 gene refers to a gene that produces the protein fibroblast growth factor receptor 3. Representative sequences of the FGFR3 gene can be found in the NCBI reference sequence: NG _ 012632.1. As defined herein, MECP2 gene refers to a gene that produces the protein methyl-CpG binding protein 2. Representative sequences of MECP2 gene can be found in NCBI reference sequence: NG _ 007107.2. As defined herein, the ATXN1 gene refers to the gene that produces the protein spinocerebellar ataxia protein (ataxin) 1. Representative sequences of the ATXN1 gene can be found in the NCBI reference sequence: NG _ 011571.1. As defined herein, the ATXN3 gene refers to the gene that produces the protein spinocerebellar ataxia protein 3. Representative sequences of the ATXN3 gene can be found in the NCBI reference sequence: NG _ 008198.2. As defined herein, the CACNA1A gene refers to a gene that produces the protein calcium voltage-gated channel subunit α 1A. Representative sequences of the CACNA1A gene can be found in the NCBI reference sequence: NG _ 011569.1. As defined herein, the ATXN7 gene refers to the gene that produces the protein spinocerebellar ataxia protein 7. Representative sequences of the ATXN7 gene can be found in the NCBI reference sequence: NG _ 008227.1. As defined herein, a TBP gene refers to a gene that produces a protein TATA-box binding protein. Representative sequences of TBP genes can be found in the NCBI reference sequence: NG _ 008165.1. As defined herein, HTT gene refers to the gene that produces the protein huntingtin. Representative sequences of HTT genes can be found in NCBI reference sequences: NG _ 009378.1. As defined herein, an AR gene refers to a gene that produces a protein androgen receptor. Representative sequences of the AR gene can be found in the NCBI reference sequence: NG _ 009014.2. As defined herein, the FXN gene refers to a gene that produces the protein mitochondrial ataxia protein (frataxin). Representative sequences of the FXN gene can be found in the NCBI reference sequence: NG _ 008845.2. As defined herein, a DMPK gene refers to a gene that produces protein DM1 protein kinase. Representative sequences of the DMPK gene can be found in the NCBI reference sequence: NG _ 009784.1. As defined herein, the PABPN1 gene refers to the gene that produces the protein poly (a) binding protein core 1. Representative sequences of PABPN1 gene can be found in NCBI reference sequence: NG _ 008239.1. As defined herein, the ATXN8 gene refers to the gene that produces the protein spinocerebellar ataxia protein 8. Representative sequences of the ATXN8 gene can be found in genomic coordinates (GRCh 38): 13:54,700,000-72,800,000.
As described herein, the term "anti-silencing partial coding sequence" refers to a partial coding sequence having a mutation compared to a homologous sequence from a corresponding endogenous gene, wherein the mutation is designed to prevent or reduce silencing by the corresponding RNAi cassette. The mutation may be an insertion, substitution or deletion of a nucleotide within the DNA sequence encoding the target RNA sequence. The mutation may be sufficient to prevent or reduce hybridization of the short RNA molecule to the RNA transcript.
As defined herein, when referring to an anti-silencing moiety coding sequence, "absence of sequence" refers to the deletion of one or more nucleotides within the corresponding RNAi target site. For example, if the RNAi targets a transcript produced by sequence GGTATCAAGACTACGAAC (within an exon of an endogenous gene), this sequence may also be present within a portion of the coding sequence of a transgene described herein. To prevent modified gene silencing, the RNAi target sequence within a portion of the coding sequence within the transgene may be modified. Specifically, a site may be mutated by insertion, substitution, or deletion of a nucleotide within the site. If the mutation is a deletion, one or more of the nucleotides may be deleted. In the case of nucleotide deletions, it is preferred that the deletion is designed as an in-frame deletion that does not eliminate the function of the protein.
As defined herein, "administering" may refer to the delivery, provision, or introduction of an exogenous molecule into a cell. If a transgene or rare-cutting endonuclease is administered to a cell, the transgene or rare-cutting endonuclease is delivered, provided, or introduced into the cell. The rare-cutting endonuclease can be administered in the form of a purified protein, a nucleic acid, or a mixture of a purified protein and a nucleic acid. The nucleic acid (i.e., RNA or DNA) can encode a rare-cutting endonuclease or a portion of a rare-cutting endonuclease (e.g., a gRNA). Administration can be accomplished by methods such as lipid-mediated transfer, electroporation, direct injection, cell fusion, particle bombardment, calcium phosphate co-precipitation, DEAE-dextran-mediated transfer, viral vector-mediated transfer, or any means suitable for delivering a purified protein or nucleic acid or a mixture of purified proteins and nucleic acids to a cell.
The percent sequence identity between a particular nucleic acid or amino acid sequence and the sequence referenced by a particular sequence identifier is determined as follows. First, a nucleic acid or amino acid sequence is compared to the sequences listed in a particular sequence identification number using the BLAST 2 sequence (Bl2seq) program from an independent version of BLASTZ containing BLASTN version 2.0.14 and BLASTP version 2.0.14. This independent version of BLASTZ can be obtained online from fr.com/blast or at ncbi.nlm.nih.gov. A description of how to use the Bl2seq program can be found in the self-describing document accompanying BLASTZ. Bl2seq performs a comparison between two sequences using the BLASTN or BLASTP algorithm. BLASTN is used to compare nucleic acid sequences, while BLASTP is used to compare amino acid sequences. To compare two nucleic acid sequences, the options are set as follows: set-i as a file containing the first nucleic acid sequence to be compared (e.g., C: \ seq1. txt); set-j to a file containing a second nucleic acid sequence to be compared (e.g., C: \ seq2. txt); setting-p to blastn; set-o to any desired file name (e.g., C: \ output.txt); setting-q to-1; -r is set to 2; and all other options are kept in the default setting. For example, the following commands may be used to generate an output file containing a comparison between two sequences: c \\ \ Bl2seq-i C: \ seq1.txt-jc: \ seq2.txt-p blastn-o C: \ output. txt-q-1-r 2. To compare two amino acid sequences, the options for the Bl2seq were set as follows: set-i as a file containing the first amino acid sequence to be compared (e.g., C: \ seq1. txt); set-j to a file containing the second amino acid sequence to be compared (e.g., C: \ seq2. txt); setting-p to blastp; set-o to any desired file name (e.g., C: \ output.txt); and all other options are kept in the default setting. For example, the following commands can be used to generate an output file containing a comparison between two amino acid sequences: c \\ \ Bl2seq-i C: \ seq1.txt-j C \ seq2.txt-p blastp-o C: \ output. If the two compared sequences share homology, the designated output file will present those regions of homology as aligned sequences. If the two compared sequences do not share homology, the designated output file will not present the aligned sequences.
Once aligned, the number of matches is determined by counting the number of positions at which the same nucleotide or amino acid residue is present in both sequences. Percent sequence identity is determined by dividing the number of matches by the length of the sequence listed in the identified sequence or the length that is articulated (e.g., 100 contiguous nucleotides or amino acid residues from the sequence listed in the identified sequence), and then multiplying the resulting value by 100. The percentage sequence identity value is rounded to the nearest tenth.
Bidirectional gene repair system with one or more promoters
In one embodiment, this document features a transgene and a method for modifying the 5' end of an endogenous gene. The transgene may include a first promoter and a second promoter, wherein the first promoter is operably linked to the first partial coding sequence and the second promoter is operably linked to the second partial coding sequence. The first and second partial coding sequences may be operably linked to a first and second splice donor sequence, respectively (fig. 1). The first promoter, first partial coding sequence, and first splice donor may be positioned in a head-to-head orientation with the second promoter, second partial coding sequence, and second splice donor. The transgene may be integrated into the endogenous gene at an intron or exon-intron junction. In some embodiments, the transgene may be integrated into an endogenous gene using a rare-cutting endonuclease or a transposon. In one embodiment, a transgene comprising a first promoter and a second promoter, a first portion and a second portion of a coding sequence, and a first splice donor and a second splice donor may be flanked by additional sequences, such as viral inverted terminal repeats (e.g., adeno-associated viral inverted repeats). These transgenes can be integrated into endogenous genes by targeting double strand breaks using rare-cutting endonucleases.
In another embodiment, a transgene comprising a first promoter and a second promoter, a first partial coding sequence and a second partial coding sequence, and a first splice donor and a second splice donor may be flanked by a first rare-cutting endonuclease target site and a second rare-cutting endonuclease target site. These transgenes can be integrated into the endogenous gene by targeting a double-strand break using one or more rare-cutting endonucleases that cleave sequences within the endogenous gene and cleave flanking target sites within the transgene.
In another embodiment, a transgene comprising a first promoter and a second promoter, a first partial coding sequence and a second partial coding sequence, and a first splice donor and a second splice donor may be flanked by a first homology arm and a second homology arm. These transgenes can be integrated into the endogenous gene by targeting a double-strand break using one or more rare-cutting endonucleases, which cleave the endogenous gene.
In another embodiment, a transgene comprising a first promoter and a second promoter, a first partial coding sequence and a second partial coding sequence, and a first splice donor and a second splice donor may be flanked by a first homology arm and a second homology arm, and a first rare-cutting endonuclease target site and a second rare-cutting endonuclease target site. These transgenes can be integrated into the endogenous gene by targeting a double-strand break using one or more rare-cutting endonucleases that cleave sequences within the endogenous gene and cleave flanking target sites within the transgene. The first and second target sites within the vector may be flanking the first and second homology arms. Alternatively, the first target site or the second target site, or both the first target site and the second target site may be within a homology arm.
In another embodiment, a transgene comprising a first promoter and a second promoter, a first portion and a second portion of a coding sequence, and a first splice donor and a second splice donor may be flanked by a left transposon end and a right transposon end. These transgenes can be integrated into endogenous genes by transposition using a transposase. As described herein, the transposase can be a CRISPR-associated transposase.
In some embodiments, the first promoter and the second promoter may be replaced with a bidirectional promoter. In other embodiments, the transgene may further include a first terminator and a second terminator positioned in a tail-to-tail orientation between the first promoter and the second promoter (fig. 1). Alternatively, the first terminator and the second terminator may be replaced with bidirectional terminators.
In one embodiment, this document features a method for modifying the 5' end of an endogenous gene, wherein the endogenous gene has at least one intron between two coding exons. The intron can be any intron that is removed from the precursor messenger RNA by conventional messenger RNA processing machinery. The intron can be between 20bp and >500kb, and includes elements comprising a splice donor site, a branching sequence, and an acceptor site. The transgenes disclosed herein for modifying the 5' end of an endogenous gene may include a number of functional elements, including a target site for a rare-cutting endonuclease, a homology arm, a splice acceptor sequence, a coding sequence, a promoter, and a transcription terminator (fig. 1).
In embodiments, the site of transgene integration may be an intron or an intron-exon junction. When targeting an intron, a portion of the coding sequence may include a sequence that encodes a peptide produced from an exon preceding the intron within the endogenous gene. For example, if the transgene is designed to integrate in intron 2 of an endogenous gene having 12 exons, then the partial coding sequence may encode peptides produced by exons 1 and 2 of the endogenous gene. When targeting the exon-intron junction, the transgene may be integrated at the exon-intron junction such that intron sequences are retained. In one embodiment, following integration, the intron sequence is retained and the upstream exon sequence is retained (i.e., the nucleotide from the transgene is added between the last nucleotide in the exon and the first nucleotide in the intron). Alternatively, in one embodiment, the intron sequence is retained, but one or more nucleotides in the exon sequence are removed after integration.
In one embodiment, the transgene comprises two target sites for a rare-cutting endonuclease. The target site may be of a sequence and length suitable for cleavage by a rare-cutting endonuclease. The target site may be cleaved by a CRISPR system, a TAL effector nuclease, a zinc finger nuclease or meganuclease or a combination of CRISPR systems, TALE nucleases, zinc finger nucleases or meganucleases or any other rare-cutting endonuclease. The target site can be located such that cleavage by the rare-cutting endonuclease causes the transgene to be released from the vector. The vector may comprise a viral vector (e.g., an adeno-associated vector) or a non-viral vector (e.g., a plasmid, a minicircle vector). If the transgene comprises two target sites, the target sites may be the same sequence (i.e., targeted by the same rare-cutting endonuclease) or they may be different sequences (i.e., targeted by two or more different rare-cutting endonucleases).
In some embodiments, a transgene provided herein can be integrated with a transposase. Transposases may include CRISPR transposases (Strecker et al, Science 10.1126/Science aax9181, 2019; Klompe et al, Nature, 10.1038/s41586-019-1323-z, 2019). The transposase can be used in combination with a transgene comprising first and second splice acceptor sequences, first and second coding sequences, a bidirectional terminator or first and second terminators (fig. 1), and transposon left and right ends. The CRISPR transposase can comprise TypeV-U5, C2C5 CRISPR protein, Cas12k, and proteins tnsB, tnsC, and tniQ. In some embodiments, Cas12k may be from P.haynaudi (Scytonemahfmani) (SEQ ID NO:30) or Anabaena (Anabaena cylindrica) (SEQ ID NO: 31). In one example, a transgene described herein comprising a left transposon end (SEQ ID NO:32) and a right transposon end (SEQ ID NO:33) can be delivered to a cell with ShCas12k, tnsB, tnsC, TniQ, and gRNA (SEQ ID NO: 44). Alternatively, the CRISPR transposase can comprise a Cas6 protein and an accessory protein comprising Cas7, Cas8, and TniQ. In one example, a transgene described herein comprising a left transposon end (SEQ ID NO:41) and a right transposon end (SEQ ID NO:43) can be delivered to a eukaryotic cell with Cas6(SEQ ID NO:37), Cas7(SEQ ID NO:36), Cas8(SEQ ID NO:35), TniQ (SEQ ID NO:34), TnsA (SEQ ID NO:38), TnsB (SEQ ID NO:39), TnsC (SEQ ID NO:40), and gRNA (SEQ ID NO: 42). These proteins may be administered directly to the cells as purified proteins, or may be encoded on RNA or DNA. If encoded on RNA or DNA, the sequences can be codon optimized for expression in eukaryotic cells. The gRNA (SEQ ID NO:42) can be placed downstream of the RNA polIII promoter and terminated with a poly (T) terminator.
In one embodiment, the transgene includes first and second target sites and first and second homology arms. The first and second homology arms can comprise sequences homologous to genomic sequences at or near the desired integration site. The length of the homology arms can be adapted to participate in homologous recombination with sequences at or near the desired integration site. Each homology arm can be between 50nt and 10,000nt in length (e.g., 50nt, 100nt, 200nt, 300nt, 400nt, 500nt, 600nt, 700nt, 800nt, 900nt, 1,000nt, 2,000nt, 3,000nt, 4,000nt, 5,000nt, 6,000nt, 7,000nt, 8,000nt, 9,000nt, 10,000 nt). In one embodiment, the homology arms can include a functional element comprising a target site for a rare-cutting endonuclease. In one embodiment, the first homology arm (e.g., the left homology arm) may include sequences homologous to targeted exons or introns, and the second homology arm may include sequences homologous to genomic sequences downstream from the first homology arm. The first homology arm must not have a splice acceptor function relative to the direction of transcription from the promoter on the transgene. To determine whether a sequence includes a splice acceptor function, several steps can be taken, including in silico analysis and experimental testing. To determine if there is potential for splice acceptor function, the desired sequence of the second homology arm can be searched for consensus branch sequences (e.g., YTRAC) and splice acceptor sites (e.g., Y-rich NCAGG). If a branched or splice acceptor sequence is present, a single nucleotide polymorphism may be introduced to disrupt function, or a different but adjacent sequence may be selected that does not include such a sequence. To experimentally determine whether the first homology arm has a splice acceptor function, synthetic constructs including the first homology arm within an intron within a reporter gene may be constructed. The construct can then be administered to the appropriate cell type and its splicing function monitored by assessing reporter gene activity.
In one embodiment, the transgene includes two splice donor sequences referred to herein as a first splice donor sequence and a second splice donor sequence. The first and second splice donor sequences are positioned in opposite directions (i.e., in a head-to-head orientation) within the transgene and flanking the internal sequences (i.e., the partial coding sequence and the promoter). When the transgene is integrated into an intron in either the forward or reverse direction, the splice donor sequence facilitates initiation of intron splicing in the corresponding pre-mRNA. The first splice donor sequence and the second splice donor sequence may be the same sequence or different sequences. One or both splice donor sequences may be that of the intron into which the transgene is to be integrated. One or both splice donor sequences may be synthetic splice donor sequences or splice donor sequences from introns of different genes.
In one embodiment, the transgene comprises first and second coding sequences operably linked to first and second splice donor sequences. The first coding sequence and the second coding sequence are positioned within the transgene in opposite directions (i.e., in head-to-head orientation). When the transgene is integrated into the endogenous gene in either the forward or reverse direction, the first and second coding sequences are transcribed into mRNA by a promoter located within the transgene. The coding sequence can be designed to correct defective coding sequences, to introduce mutations or to introduce new peptide sequences. The first coding sequence and the second coding sequence may be the same nucleic acid sequence and encode the same protein. Alternatively, the first coding sequence and the second coding sequence may be different nucleic acid sequences and encode the same protein (i.e., using degeneracy of codons). The coding sequence may encode a purification tag (e.g., glutathione-S-transferase, poly (His), maltose binding protein, Strep-tag, Myc-tag, AviTag, HA-tag, or chitin binding protein) or a reporter protein (e.g., GFP, RFP, lacZ, cat, luciferase, puro, neomycin).
In one embodiment, the methods and compositions described herein can be used to modify the 5' end of an endogenous gene, thereby causing a modification of the N-terminus of the protein encoded by the endogenous gene. The modification of the 5' end of the coding sequence of the endogenous gene may comprise the replacement of the first coding exon up to the exon between the first exon and the last exon. For example, if a gene includes 12 exons, the modification may comprise the substitution of exons 1, or 1-2, or 1-3, or 1-4, or 1-5, or 1-6, or 1-7, or 1-8, or 1-9, or 1-10, or 1-11. In one embodiment, the replaced endogenous exon may be replaced with a similar sequence. For example, the first coding sequence or the second coding sequence of a transgene may include exons 1, or 1-2, or 1-3, or 1-4, or 1-5, or 1-6, or 1-7, or 1-8, or 1-9, or 1-10, or 1-11. The transgene may be integrated into an intron downstream of an exon in the endogenous gene, which is the last exon within the coding sequence of the transgene (fig. 3). Alternatively, the transgene may be integrated within an exon corresponding to the last exon within the transgene coding sequence (fig. 8). The transgene can be designed to be 4.7kb or smaller and incorporated into AAV vectors and particles, and then delivered to target cells in vivo.
In one embodiment, a transgene may include a bi-directional promoter or a first promoter and a second promoter operably linked to a first coding sequence and a second coding sequence. The bidirectional promoter or the first promoter and the second promoter are positioned in opposite directions (i.e., in head-to-head orientation) within the transgene. The bidirectional promoter or the first and second promoters initiate transcription of the first and second coding sequences when the transgene is integrated into the endogenous gene in the forward or reverse direction. The first promoter and the second promoter may be the same promoter or different promoters.
In one embodiment, a transgene may include a bi-directional promoter or a first promoter and a second promoter operably linked to a first coding sequence and a second coding sequence. The bidirectional promoter or the first promoter and the second promoter are positioned in opposite directions (i.e., in head-to-head orientation) within the transgene. The bidirectional promoter or the first and second promoters initiate transcription of the first and second coding sequences when the transgene is integrated into the endogenous gene in the forward or reverse direction. The first promoter and the second promoter may be the same promoter or different promoters. The promoter may be selected from, for example, CMV, EF1 α, SV40, PGK1, Ubc, human β actin, CAG, or any promoter with sufficient activity to initiate transcription of a portion of the coding sequence. Without being bound by theory, a promoter in reverse orientation may cause the production of double stranded RNA, resulting in silencing of gene expression upstream of the integration site. Further, a promoter in a forward orientation can initiate transcription of an RNA that is not subject to the same silencing (e.g., due to codon degeneracy of the coding sequence). Also described herein are methods for reducing potential RNAi from RNA produced by a promoter in the reverse orientation (figure 5).
In one embodiment, the transgene may include a bidirectional terminator or a first terminator and a second terminator interposed between the first promoter and the second promoter (fig. 1). The bidirectional terminator or the first terminator and the second terminator are positioned within the transgene in opposite directions (i.e., in a tail-to-tail orientation). When the transgene is integrated into the endogenous gene in the forward or reverse direction, the bidirectional terminator or the first terminator and the second terminator terminate transcription from the promoter of the endogenous gene. The first terminator and the second terminator may be the same terminator or different terminators.
In one embodiment, this document provides a transgene comprising first and second rare-cutting endonuclease target sites, first and second splice donor sequences, first and second coding sequences, and a bidirectional promoter or first and second promoters. The transgene may be integrated into the endogenous gene by homology-independent methods including non-homologous end joining and alternative non-homologous end joining, or by micro-homology-mediated end joining. In one aspect, the transgene is integrated into an intron within the endogenous gene (fig. 2).
In another embodiment, this document provides a transgene comprising first and second homologous arms, first and second rare-cutting endonuclease target sites, first and second splice donor sequences, first and second coding sequences, and a bidirectional promoter or first and second promoters. Transgenes can be integrated into endogenous genes by homology-dependent methods (e.g., synthesis-dependent strand annealing and micro-homology-mediated end joining) and homology-independent methods (e.g., non-homologous end joining and alternative non-homologous end joining). In one aspect, the transgene is integrated into an intron within the endogenous gene (fig. 3). In another aspect, the transgene is integrated within an exon of an endogenous gene (fig. 8).
In another embodiment, this document provides a transgene comprising first and second homology arms, first and second splice donor sequences, first and second coding sequences, and a bidirectional promoter or first and second promoters (fig. 1). In another embodiment, this document provides a transgene comprising first and second coding sequences, first and second splice donor sequences, and a bidirectional promoter or first and second promoters.
In another embodiment, this document provides a transgene comprising first and second homology arms, first and second coding sequences, first and second splice donor sequences, a bidirectional terminator or first and second terminators, and first and second additional sequences (fig. 1). The additional sequence may be any additional sequence present at the 5 'and 3' ends on the transgene, however, the additional sequence should not include any elements that act as splice acceptors or splice donors. The additional sequences may be, for example, inverted terminal repeats of the adeno-associated viral genome or left and right transposon ends.
In another embodiment, this document provides a transgene within a viral vector (including adeno-associated virus and adenovirus), wherein the transgene comprises first and second splice donor sequences, first and second coding sequences, and a bidirectional terminator or first and second terminators. The transgene also includes a first additional sequence and a second additional sequence due to the inverted terminal repeat sequence of the viral vector.
In another embodiment, this document provides a transgene within a viral vector (comprising an adeno-associated virus and an adenovirus), wherein the transgene comprises first and second homology arms, first and second splice donor sequences, first and second coding sequences, and a bidirectional promoter or first and second promoters. The transgene also includes a first additional sequence and a second additional sequence due to the inverted terminal repeat sequence of the viral vector.
In another aspect, transgenes for integration may be designed to integrate through multiple repair pathways, while producing the desired effect for each result. For example, a transgene can include first and second arm homology arms, first and second rare-cutting endonuclease target sites, first and second coding sequences, first and second promoters, and can be carried within an AAV genome (i.e., flanked by 145 nucleotide inverted terminal repeats). Following expression by the rare-cutting endonuclease, the following results may occur: 1) integrating the entire AAV genome at the target site in a forward or reverse orientation via NHEJ, 2) integrating a sequence between the first rare-cutting endonuclease target site and the second rare-cutting endonuclease target site at the target site in a forward or reverse orientation via NHEJ, 3) integrating via HR using the first and second homology arms, or 4) any combination of the above. Upon integration with any of the above results, the transgenes described herein can correct or alter the protein sequence produced by the endogenous gene.
In some embodiments, a transgene described herein can have a combination of elements comprising a splice donor, partial coding sequences, a promoter, homology arms, left and right transposase ends, and a site for cleavage by a rare-cutting endonuclease. In one embodiment, the combination may be from 5 'to 3'.
In some embodiments, a transgene described herein can have a combination of elements comprising a splice acceptor, a partial coding sequence, a terminator, a homology arm, left and right transposase ends, and a site for cleavage by a rare-cutting endonuclease.
In one embodiment, the combination from 5 'to 3' may be [ splice donor 1RC ] - [ partial coding sequence 1RC ] - [ promoter 2] - [ partial coding sequence 2] - [ splice donor 2], wherein RC represents the reverse complement. This combination can be carried on a linear DNA molecule or AAV molecule and can be integrated by targeted disruption of the target gene by NHEJ.
In another example, the combination can be from 5 'to 3' [ rare-cutting endonuclease cleavage site 1] - [ splice donor 1RC ] - [ partial coding sequence 1RC ] - [ promoter 2] - [ partial coding sequence 2] - [ splice donor 2] - [ rare-cutting endonuclease cleavage site 2 ].
In another example, the combination can be from 5 'to 3' from [ rare-cutting endonuclease cleavage site 1] - [ homology arm 1] - [ splice donor 1RC ] - [ partial coding sequence 1RC ] - [ promoter 2] - [ partial coding sequence 2] - [ splice donor 2] - [ homology arm 2] - [ rare-cutting endonuclease cleavage site 2 ]. In such a combination, one or more rare-cutting endonucleases can be used to promote HR and NHEJ. For example, a single rare cutting nuclease can cut the target gene (i.e., the desired intron), and the cleavage sites flanking the homology arms can be designed as the same target sequence within the intron.
In another example, the combination can be from 5 'to 3' [ homologous arm 1+ rare-cutting endonuclease cleavage site 1] - [ splice donor 1RC ] - [ partial coding sequence 1RC ] - [ promoter 2] - [ partial coding sequence 2] - [ splice donor 2] - [ homologous arm 2] - [ rare-cutting endonuclease cleavage site 2 ]. In this combination, one or more rare-cutting endonucleases can promote HR and NHEJ. For example, a single rare cutting nuclease can cut within homology arm 1, downstream of homology arm 2, and at a genomic target site (i.e., a site with homology to the sequence in homology arm 1).
In another example, the combination can be from 5 'to 3' [ left terminus of transposase ] - [ splice donor 1RC ] - [ partial coding sequence 1RC ] - [ promoter 2] - [ partial coding sequence 2] - [ splice donor 2] - [ right terminus of transposase ]. In all embodiments, splice donor 1 and splice donor 2 can be the same or different sequences; the partial coding sequence 1 and the partial coding sequence 2 may be the same or different sequences; promoter 1 and promoter 2 may be the same or different sequences.
In embodiments, a transgene comprising the structure [ rare-cutting endonuclease cleavage site 1] - [ homologous arm 1] - [ splice donor 1RC ] - [ partial coding sequence 1] - [ promoter 1RC ] - [ promoter 2] - [ partial coding sequence 2] - [ splice donor 2] - [ homologous arm 2] - [ rare-cutting endonuclease cleavage site 2] can be integrated into DNA by delivery of one or more rare-cutting endonucleases. If a rare-cutting endonuclease is delivered, the rare-cutting endonuclease can release the transgene by cleaving at rare-cutting endonuclease cleavage sites 1 and 2. Further, the same rare-cutting endonuclease can generate a break in the target gene, thereby mimicking insertion by HR or NHEJ.
In other embodiments, a transgene comprising the structure [ homologous arm 1+ rare-cutting endonuclease cleavage site 1] - [ splice donor 1RC ] - [ partial coding sequence 1] - [ promoter 1RC ] - [ promoter 2] - [ partial coding sequence 2] - [ splice donor 2] - [ homologous arm 2] - [ rare-cutting endonuclease cleavage site 1] can be integrated into the DNA by delivery of one or more rare-cutting endonucleases. If a rare-cutting endonuclease is delivered, the rare-cutting endonuclease can release the transgene by cleaving at rare-cutting endonuclease cleavage sites 1 and 2. Further, the same rare-cutting endonuclease can generate a break in the target gene, thereby mimicking insertion by HR or NHEJ. When cleavage is upstream of the integration site (i.e., within the homology arm), integration can occur via HR.
In embodiments, a codon adjustment may be made to a portion of the coding sequence. Codon adjustments may be aimed at 1) reducing double-stranded RNA pairing (fig. 5) and 2) optimizing protein expression. Double-stranded RNA can be produced if a transgene comprising a first and a second coding part operably linked to a first and a second promoter is integrated into an endogenous gene, and the first and second coding parts are homologous to each other and to the endogenous gene (fig. 5). Codon adjustments may be made to portions of the coding sequence to minimize RNA pairing. In one embodiment, the codon optimization may be complete and distinct for the first partial coding sequence and the second partial coding sequence. For example, the partial coding sequence 1 may have a different nucleotide sequence than the partial coding sequence 2, and both partial coding sequences 1 and 2 may be sequences that differ from the corresponding sequences within the endogenous gene of interest.
In another embodiment, codon optimization may be separated between the first and second partial coding sequences. For example, the first partial coding sequence may have a mixture of non-codon-regulated sequences (i.e., homologous to corresponding sequences within the endogenous gene of interest) and codon-regulated sequences. In this example, the second partial code sequence may have the opposite adjustment. For example, in the 200 nucleotide partial coding sequences 1 and 2, the partial coding sequence 1 nucleotides 1-100 and the endogenous gene of interest within the sequence homology, and the nucleotides 101-200 can be codon adjusted to the endogenous gene of interest with minimal sequence similarity; nucleotides 1-100 of the partial coding sequence 2 may be codon adjusted to have minimal sequence similarity to the endogenous gene of interest, and nucleotides 101-200 may be homologous to sequences within the endogenous gene of interest.
In one embodiment, the genomic modification is the insertion of a transgene into the endogenous ATXN2 genomic sequence. The transgene may comprise part of the coding sequence of ATXN2 protein. The partial coding sequence may be homologous to the coding sequence within the wild-type ATXN2 gene or a functional variant of the wild-type ATXN2 gene, a codon-regulated version of the ATXN2 gene or a mutated ATXN2 gene. In one example, a transgene encoding part of the ATXN2 protein was inserted into intron 1 of the endogenous ATXN2 gene (fig. 3 and 4).
In one embodiment, the transgene provided herein comprises a first and second partial coding sequence that encodes a peptide produced by exon 1 of the ATXN2 gene (fig. 7). The transgene may be integrated within intron 1 or at the exon 1 intron 1 junction within the endogenous ATXN2 gene. This embodiment is particularly useful in cells that include an expanded trinucleotide repeat sequence in exon 1 of ATXN 2.
The methods and compositions provided herein can be used to modify genes encoding intracellular proteins. Endogenous proteins may include fibrinogen, prothrombin, tissue factor, factor V, factor VII, factor VIII, factor IX, factor X, factor XI, factor XII (Hageman factor), factor XIII (fibrin-stabilizing factor), von Willebrand factor, prekallikrein, high molecular weight kininogen (Fitzgerald factor), fibronectin, antithrombin III, heparin cofactor II, protein C, protein S, protein Z-related protease inhibitors, plasminogen, alpha 2-antiplasmin, tissue plasminogen activator, urokinase, plasminogen activator inhibitor-1, plasminogen activator inhibitor-2, Glucocerebrosidase (GBA), alpha-galactosidase A (GLA), iduronate sulfatase (IDS), Iduronidase (IDUA), acid sphingomyelinase (SMPD1), MMAA, MMAB, MMACHC, MMADHC (C2orf25), MTRR, LMBRD1, MTR, propionyl-coa carboxylase (PCC) (PCCA and/or PCCB subunits), glucose-6-phosphate transporter (G6PT) protein or glucose-6-phosphatase (G6Pase), LDL receptor (LDLR), ApoB, LDLRAP-1, PCSK9, mitochondrial proteins such as NAGS (N-acetylglutamate synthetase), CPS1 (carbamoylphosphate synthetase I) and OTC (ornithine transcarbamylase), ASS (argininosuccinate synthetase), ASL (argininosuccinate lyase) and/or ARG1 (arginase) and/or the solute carrier family 25 (25 a13, aspartate/glutamate carrier) protein, UGT1a1 or glucuronyl-a polypeptide 1, acetyltransferase (UDP h) acetyltransferase (PCCA and/or PCCB subunits), glucuronate transporter (N6-acetyl-6-phosphate synthetase), CPS1 (ornithine transcarbamate), ASS (LDLR), ASS (arginase), ASL (argininosuccinate synthetase), ASL (arginase I) and/or OTC (argininosuccinate) enzyme, Alanine-glyoxylate Aminotransferase (AGXT) protein, glyoxylate reductase/hydroxypyruvate reductase (GRHPR) protein, transthyretin gene (TTR) protein, ATP7B protein, phenylalanine hydroxylase (PAH) protein, USH2A protein, ATXN protein, and lipoprotein lyase (LPL) protein.
The transgene may comprise a sequence for modifying an endogenous gene carrying a loss-of-function or gain-of-function mutation. The mutations may comprise mutations that result in the following genetic diseases: achondroplasia, achromatopsia, acid maltase deficiency, adenosine deaminase deficiency, adrenoleukodystrophy, eccardi syndrome (acardi syndrome), alpha-1 antitrypsin deficiency, alpha-thalassemia, androgen insensitive syndrome, pert syndrome (pert syndrome), arrhythmogenic right ventricular dysplasia, ataxia telangiectasia, barth syndrome, beta-thalassemia, blue rubber blister syndrome, canavan disease, Chronic Granulomatous Disease (CGD), crinis syndrome, cystic fibrosis, de-ken's disease, ectodermal dysplasia, fanconi anemia, progressive ossification fibrodysplasia, fragile X syndrome, galactose, generalized gangliosidosis (e.g., GM1), hemochromatosis, haemoglobin C mutation at codon 6 of beta-globin (HbC), haemophilia, Huntington's chorea, hypophosphatemia, Klinefelter syndrome, Kraberra Disease (Krabes Disease), Langer-Giedion syndrome, leucocyte adhesion deficiency, leukodystrophy, Long QT syndrome, Marfan syndrome, Mobies syndrome, Mucopolysaccharidosis (MPS), ungula syndrome, nephrodiabetes insipidus, neurofibromatosis, Neiman-Pick Disease, osteogenesis imperfecta, porphyria, Prader-Willi syndrome (Prader-Willi syndrome), progeria, Prader syndrome (Proteus drome), retinoblastoma, syndranthesis syndrome (synthetic syndrome), Thinle-Willi syndrome (Tailex-draw syndrome), progeria syndrome (Tailex syndrome), Safeilibo syndrome (Sanfilippo syndrome), Severe Combined Immunodeficiency (SCID), Schwarckman syndrome (Shwachman syndrome), sickle cell disease (sickle cell anemia), Smith-Magenis syndrome, Steckel syndrome (Stickler syndrome), Tay-Sachs disease (Tay-Sachs disease), Thrombocytopenia radial deficiency (Thrombocytopenia Absent Radius, TAR) syndrome, Trader Coriolis syndrome (Treacher Collins syndrome), trisomy, tuberous sclerosis, Trader's syndrome, Urea circulatory disorder, von Hippel-Landau disease, Waardenberg syndrome (Waardenwarwery syndrome), Holsis syndrome (Williams syndrome), Willison's syndrome, Williams ' syndrome, Witkoff's syndrome (Willd-Willd syndrome), Skinson's disease, Wilford-Aldrich syndrome (Aldrich lymphoproliferative syndrome), gaucher's disease, GM1, Fabry disease and tay-sachs disease, von Willebrand disease, usher syndrome, polycystic kidney disease, spinocerebellar ataxia type 2, spinal and bulbar muscular atrophy, Friedreich's ataxia, and myotonic dystrophy type 2.
As described herein, the transgene may be carried within a viral or non-viral vector. The vector may be in the form of circular or linear double-stranded or single-stranded DNA. The donor molecule may be conjugated or associated with an agent that promotes stability or cell renewal. The agent may be a lipid, calcium phosphate, cationic polymer, DEAE-dextran, dendrimer, polyethylene glycol (PEG) cell penetrating peptide, gas-encapsulated microbubbles, or magnetic beads. The donor molecule may be incorporated into a viral particle. The virus may be a retrovirus, adenovirus, adeno-associated vector (AAV), herpes simplex, poxvirus, hybrid adenovirus vector, epstein-bar virus (epstein-bar virus), lentivirus, or herpes simplex virus.
Gene repair system with RNAi cassette
In another example, the methods described herein can be used to silence endogenous genes while replacing lost RNA/protein due to silencing. In one embodiment, the method may comprise administering a transgene to a cell, wherein the transgene comprises two functional elements: 1) a silencing sequence and 2) a complete coding sequence that encodes a protein homologous to the silencing protein (FIG. 9), but is resistant to silencing. The two functional elements may be on separate transgenes or on the same transgene. In another embodiment, the method can comprise administering a transgene to a cell, wherein the transgene is integrated into an endogenous gene of interest and comprises 1) a silencing sequence and 2) a partial or complete coding sequence for repairing the mutated gene but that is resistant to silencing (fig. 12-17).
The silencing sequence may include a promoter, a nucleic acid sequence for silencing the target nucleic acid, and a terminator. The nucleic acid sequence can be in a form capable of inducing gene silencing within a target nucleic acid (e.g., a microrna, a hairpin RNA, an antisense RNA). The nucleic acid sequence may target different regions in the mRNA of the target gene, including the 5 'UTR, coding sequence, or 3' UTR.
In one embodiment, this document describes a method for silencing and replacing the production of a protein of interest by administering the transgene described in fig. 13 to a cell and integrating the transgene into an endogenous gene of interest. In one embodiment, a transgene may include a splice acceptor, a partial coding sequence (which is resistant to silencing), a terminator, and an RNAi cassette designed to silence an endogenous gene of interest. The splice acceptor may be operably linked to a portion of the coding sequence, which may be operably linked to a terminator. The splice acceptor, partial coding sequence, terminator and RNAi cassette may be flanked by a first and second homology arm or a left transposon end and a right transposon end. The transgene may be integrated into an intron within the endogenous gene of interest or at an intron-exon junction within the endogenous gene of interest. Relative to the location of transgene integration, a portion of the coding sequence may encode the remaining peptide sequence. For example, if the transgene is integrated into intron 3 of a gene that includes 5 exons (fig. 13), then a portion of the coding sequence may encode peptides produced by exons 4 and 5 of the endogenous gene. The RNAi cassettes in these transgenes can target sequences within exons 4 or 5 or the 3' UTR. Thus, corresponding target sites within portions of the coding sequence within the transgene may be modified to prevent silencing of the modified endogenous allele. In other embodiments, the transgene may include a first splice acceptor and a second splice acceptor, a first portion of a coding sequence and a second portion of a coding sequence (both resistant to silencing), a first terminator and a second terminator, and an RNAi cassette. These transgenes may be flanked by additional sequences (e.g., viral ITRs), first and second rare-cutting endonuclease target sites, left and right transposon ends or first and second homology arms, and first and second rare-cutting endonuclease target sites. In one embodiment, the transgene construct may be [ homology arm 1] - [ splice acceptor ] - [ partial coding sequence ] - [ terminator ] - [ RNAi cassette ] - [ homology arm 2] from 5 'to 3'. In another example, the transgene construct may be [ transposase left end ] - [ splice acceptor ] - [ partial coding sequence ] - [ terminator ] - [ RNAi cassette ] - [ transposase right end ] from 5 'to 3'. In another example, the transgene construct may be [ alternative sequence 1] - [ splice acceptor 1] - [ partial coding sequence 1] - [ terminator 1] - [ RNAi cassette ] - [ terminator 2RC ] - [ partial coding sequence 2RC ] - [ splice acceptor 2RC ] - [ alternative sequence 2] from 5 'to 3'. In another example, the transgene construct may be [ rare-cutting endonuclease target site 1] - [ splice acceptor 1] - [ partial coding sequence 1] - [ terminator 1] - [ RNAi cassette ] - [ terminator 2RC ] - [ partial coding sequence 2RC ] - [ splice acceptor 2RC ] - [ rare-cutting endonuclease target site 2] from 5 'to 3'. In another example, the transgene construct may be [ rare-cutting endonuclease target site 1] - [ homology arm 1] - [ splice acceptor 1] - [ partial coding sequence 1] - [ terminator 1] - [ RNAi cassette ] - [ terminator 2RC ] - [ partial coding sequence 2RC ] - [ splice acceptor 2RC ] - [ homology arm 2] - [ rare-cutting endonuclease target site 2] from 5 'to 3'. In another embodiment, the transgene construct may be [ transposase left end ] - [ splice acceptor 1] - [ partial coding sequence 1] - [ terminator 1] - [ RNAi cassette ] - [ terminator 2RC ] - [ partial coding sequence 2RC ] - [ splice acceptor 2RC ] - [ transposase right end ] from 5 'to 3'.
In one embodiment, this document describes a method for silencing and replacing the production of a protein of interest by administering the transgene described in fig. 14 to a cell and integrating the transgene into an endogenous gene of interest. In one embodiment, a transgene may include a splice acceptor, a 2A sequence, the entire coding sequence (which is resistant to silencing), a terminator, and an RNAi cassette designed to silence an endogenous gene of interest. The splice acceptor can be operably linked to a 2A sequence that can be operably linked to the complete coding sequence, which can be operably linked to a terminator. The splice acceptor, 2A sequence, complete coding sequence, terminator and RNAi cassette may be flanked by a first and a second homology arm or a left and a right transposon end. The transgene may be integrated into an intron within the endogenous gene of interest or at an intron-exon junction within the endogenous gene of interest (fig. 14). RNAi can be designed to silence the expression of an endogenous gene of interest, and the entire coding sequence within a transgene can be designed to be resistant to silencing. Thus, the corresponding target site within the complete coding sequence within the transgene can be modified to prevent silencing. In other embodiments, the transgene may include a first splice acceptor and a second splice acceptor, a first and a second 2A sequence, a first coding sequence and a second coding sequence (both resistant to silencing), a first terminator and a second terminator, and an RNAi cassette. These transgenes may be flanked by additional sequences (e.g., viral ITRs), first and second rare-cutting endonuclease target sites, left and right transposon ends or first and second homology arms, and first and second rare-cutting endonuclease target sites. In one embodiment, the transgene construct may be [ homology arm 1] - [ splice acceptor ] - [2A ] - [ coding sequence ] - [ terminator ] - [ RNAi cassette ] - [ homology arm 2] from 5 'to 3'. In another embodiment, the transgene construct may be [ transposase left end ] - [ splice acceptor ] - [2A ] - [ coding sequence ] - [ terminator ] - [ RNAi cassette ] - [ transposase right end ] from 5 'to 3'. In another example, the transgene construct may be [ alternative sequence 1] - [ splice acceptor 1] - [2A1] - [ coding sequence 1] - [ terminator 1] - [ RNAi cassette ] - [ terminator 2Rc ] - [ coding sequence 2Rc ] - [ splice acceptor 2Rc ] - [ alternative sequence 2] from 5 'to 3'. In another example, the transgene construct may be [ rare-cutting endonuclease target site 1] - [ splice acceptor 1] - [2A1] - [ coding sequence 1] - [ terminator 1] - [ RNAi cassette ] - [ terminator 2RC ] - [ coding sequence 2RC ] - [2 A2 RC ] - [ splice acceptor 2RC ] - [ rare-cutting endonuclease target site 2] from 5 'to 3'.
In another example, the transgene construct can be [ rare-cutting endonuclease target site 1] - [ homology arm 1] - [ splice acceptor 1] - [2A1] - [ coding sequence 1] - [ terminator 1] - [ RNAi cassette ] - [ terminator 2RC ] - [ coding sequence 2RC ] - [2 A2 RC ] - [ splice acceptor 2RC ] - [ homology arm 2] - [ rare-cutting endonuclease target site 2] from 5 'to 3'. In another embodiment, the transgene construct may be [ transposase left end ] - [ splice acceptor 1] - [2a1] - [ coding sequence 1] - [ terminator 1] - [ RNAi cassette ] - [ terminator 2RC ] - [ coding sequence 2RC ] - [2 A2 RC ] - [ splice acceptor 2RC ] - [ transposase right end ] from 5 'to 3'.
In one embodiment, this document describes a method for silencing and replacing the production of a protein of interest by applying the transgene described in fig. 15 to a cell and integrating the transgene into an endogenous gene of interest. In one embodiment, a transgene can include a 2A sequence, a complete coding sequence (which is resistant to silencing), a terminator, and an RNAi cassette designed to silence an endogenous gene of interest. The 2A sequence may be operably linked to a complete coding sequence, which may be operably linked to a terminator. The 2A sequence, complete coding sequence, terminator and RNAi cassette may be flanked by a first and second homology arm or left and right transposon ends. The transgene may be integrated into an exon within the endogenous gene of interest (fig. 15). RNAi can be designed to silence the expression of an endogenous gene of interest, and the entire coding sequence within a transgene can be designed to be resistant to silencing. Thus, the corresponding target site within the complete coding sequence within the transgene can be modified to prevent silencing. In other embodiments, the transgene can include first and second 2A sequences, first and second coding sequences (both resistant to silencing), first and second terminators, and an RNAi cassette. These transgenes may be flanked by additional sequences (e.g., viral ITRs), first and second rare-cutting endonuclease target sites, left and right transposon ends or first and second homology arms, and first and second rare-cutting endonuclease target sites. In one embodiment, the transgene construct may be [ homology arms 1] - [2A ] - [ coding sequence ] - [ terminator ] - [ RNAi cassette ] - [ homology arms 2] from 5 'to 3'. In another embodiment, the transgene construct may be [ transposase left end ] - [2A ] - [ coding sequence ] - [ terminator ] - [ RNAi cassette ] - [ transposase right end ] from 5 'to 3'. In another example, the transgene construct may be [ additional sequence 1] - [2A1] - [ coding sequence 1] - [ terminator 1] - [ RNAi cassette ] - [ terminator 2RC ] - [ coding sequence 2RC ] - [2 A2 RC ] - [ additional sequence 2] from 5 'to 3'. In another example, the transgene construct can be [ rare-cutting endonuclease target site 1] - [2A1] - [ coding sequence 1] - [ terminator 1] - [ RNAi cassette ] - [ terminator 2RC ] - [ coding sequence 2RC ] - [2 A2 RC ] - [ rare-cutting endonuclease target site 2] from 5 'to 3'. In another example, the transgene construct can be [ rare-cutting endonuclease target site 1] - [ homology arms 1] - [2A1] - [ coding sequence 1] - [ terminator 1] - [ RNAi cassette ] - [ terminator 2RC ] - [ coding sequence 2RC ] - [2 A2 RC ] - [ homology arms 2] - [ rare-cutting endonuclease target site 2] from 5 'to 3'. In another embodiment, the transgene construct may be [ transposase left end ] - [2A1] - [ coding sequence 1] - [ terminator 1] - [ RNAi cassette ] - [ terminator 2RC ] - [ coding sequence 2RC ] - [2 A2 RC ] - [ transposase right end ] from 5 'to 3'.
In one embodiment, this document describes a method for silencing and replacing the production of a protein of interest by applying the transgene described in fig. 16 to a cell and integrating the transgene into an endogenous gene of interest. In one embodiment, a transgene can include the entire coding sequence (which is resistant to silencing and includes an initiation codon), a terminator, and an RNAi cassette designed to silence an endogenous gene of interest. The complete coding sequence may be operably linked to a terminator. The complete coding sequence, terminator and RNAi cassette can be flanked by a first and second homology arm or a left transposon end and a right transposon end. The integration site may be within the 5' UTR but before the start codon (figure 16). If additional integration sites are present, the additional integration sites may be within an intron within the 5' UTR; however, the transgene described in this example need to include a splice acceptor sequence operably linked to one or more entire coding sequences. RNAi can be designed to silence the expression of an endogenous gene of interest, and the entire coding sequence within a transgene can be designed to be resistant to silencing. Thus, the corresponding target site within the complete coding sequence within the transgene can be modified to prevent silencing. In other embodiments, a transgene can include a first coding sequence and a second coding sequence (both resistant to silencing), a first terminator and a second terminator, and an RNAi cassette. These transgenes may be flanked by additional sequences (e.g., viral ITRs), first and second rare-cutting endonuclease target sites, left and right transposon ends or first and second homology arms, and first and second rare-cutting endonuclease target sites. In one embodiment, the transgene construct may be [ homology arm 1] - [ coding sequence ] - [ terminator ] - [ RNAi cassette ] - [ homology arm 2] from 5 'to 3'. In another example, the transgene construct may be [ transposase left end ] - [ coding sequence ] - [ terminator ] - [ RNAi cassette ] - [ transposase right end ] from 5 'to 3'. In another example, the transgene construct may be [ additional sequence 1] - [ coding sequence 1] - [ terminator 1] - [ RNAi cassette ] - [ terminator 2RC ] - [ coding sequence 2RC ] - [ additional sequence 2] from 5 'to 3'. In other embodiments, the transgene may be designed to replace protein production and not silence endogenous genes. In one embodiment, the transgene construct may be [ rare-cutting endonuclease target site 1] - [ coding sequence 1] - [ terminator 2RC ] - [ coding sequence 2RC ] - [ rare-cutting endonuclease target site 2] from 5 'to 3'. In another example, the transgene construct can be [ rare-cutting endonuclease target site 1] - [ homology arms 1] - [ coding sequence 1] - [ terminator 2RC ] - [ coding sequence 2RC ] - [ homology arms 2] - [ rare-cutting endonuclease target site 2] from 5 'to 3'. In another embodiment, the transgene construct may be [ transposase left end ] - [ coding sequence 1] - [ terminator 2RC ] - [ coding sequence 2RC ] - [ transposase right end ] from 5 'to 3'. In another embodiment, the transgene construct may be [ homology arm 1] - [ coding sequence ] - [ terminator ] - [ homology arm 2] from 5 'to 3'. In another embodiment, the transgene construct may be [ left-end of transposase ] - [ coding sequence ] - [ terminator ] - [ right-end of transposase ] from 5 'to 3'. In another example, the transgene construct may be [ additional sequence 1] - [ coding sequence 1] - [ terminator 2RC ] - [ coding sequence 2RC ] - [ additional sequence 2] from 5 'to 3'. In another example, the transgene construct may be [ rare-cutting endonuclease target site 1] - [ coding sequence 1] - [ terminator 2RC ] - [ coding sequence 2RC ] - [ rare-cutting endonuclease target site 2] from 5 'to 3'. In another example, the transgene construct can be [ rare-cutting endonuclease target site 1] - [ homology arms 1] - [ coding sequence 1] - [ terminator 2RC ] - [ coding sequence 2RC ] - [ homology arms 2] - [ rare-cutting endonuclease target site 2] from 5 'to 3'. In another embodiment, the transgene construct may be [ transposase left end ] - [ coding sequence 1] - [ terminator 2RC ] - [ coding sequence 2RC ] - [ transposase right end ] from 5 'to 3'.
In one embodiment, this document describes a method for silencing and replacing the production of a protein of interest by applying the transgene described in fig. 17 to a cell and integrating the transgene into an endogenous gene of interest. In one embodiment, a transgene may include an RNAi cassette designed to silence an endogenous gene, a promoter, a partial coding sequence (which is resistant to silencing), and a splice donor sequence. The promoter may be operably linked to a partial coding sequence, which may be operably linked to a splice donor. The RNAi cassette, promoter, partial coding sequence, and splice donor may be flanked by a first homology arm and a second homology arm or a left transposon end and a right transposon end. The transgene may integrate into an exon or intron within the endogenous gene of interest (fig. 17), but not into the site of disruption of the endogenous splice acceptor necessary to produce the full-length protein. RNAi can be designed to silence the expression of an endogenous gene of interest, and portions of the coding sequence within a transgene can be designed to be resistant to silencing. Thus, the corresponding target site within the complete coding sequence within the transgene can be modified to prevent silencing. In other embodiments, a transgene may include first and second splice donor sequences, first and second portions of coding sequences (both resistant to silencing), first and second promoters, and an RNAi cassette. These transgenes may be flanked by additional sequences (e.g., viral ITRs), first and second rare-cutting endonuclease target sites, left and right transposon ends or first and second homology arms, and first and second rare-cutting endonuclease target sites. In one embodiment, the transgene construct may be [ homology arm 1] - [ RNAi cassette ] - [ promoter ] - [ partial coding sequence ] - [ splice donor ] - [ homology arm 2] from 5 'to 3'. In another example, the transgene construct may be [ left end of transposon ] - [ RNAi cassette ] - [ promoter ] - [ partial coding sequence ] - [ splice donor ] - [ right end of transposon ] from 5 'to 3'. In another example, the transgene construct may be [ additional sequence 1] - [ splice donor 1Rc ] - [ partial coding sequence 1Rc ] - [ promoter 1Rc ] - [ RNAi cassette ] - [ promoter 2] - [ partial coding sequence 2] - [ splice donor 2] - [ additional sequence 2] from 5 'to 3'. In another example, the transgene construct may be [ rare-cutting endonuclease target site 1] - [ splice donor 1Rc ] - [ partial coding sequence 1Rc ] - [ promoter 1Rc ] - [ RNAi cassette ] - [ promoter 2] - [ partial coding sequence 2] - [ splice donor 2] - [ rare-cutting endonuclease target site 2] from 5 'to 3'. In another example, the transgene construct may be [ rare-cutting endonuclease target site 1] - [ homologous arm 1] - [ splice donor 1Rc ] - [ partial coding sequence 1Rc ] - [ promoter 1Rc ] - [ RNAi cassette ] - [ promoter 2] - [ partial coding sequence 2] - [ splice donor 2] - [ rare-cutting endonuclease target site 2] from 5 'to 3'. In another example, the transgene construct may be [ the left terminus of the transposase ] - [ splice donor 1RC ] - [ partial coding sequence 1RC ] - [ promoter 1RC ] - [ RNAi cassette ] - [ promoter 2] - [ partial coding sequence 2] - [ splice donor 2] - [ right terminus of the transposase ] from 5 'to 3'. Transgenes may be used to modify the SNCA gene. Mutations in SNCA have been found to cause parkinson's disease. The transgenes described herein can be used to correct SNCA gene expression. In some cases, SNCA is repeated or repeated three times, resulting in overproduction of a-synuclein. In other cases, mutations such as Ala30Pro will cause misfolding of the protein. The transgenes described herein provide a method of reducing the expression of endogenous SNCA expression (from gene duplication and intragenic mutations) while replacing the expression of SNCA with some or all of the SNCA isoforms (at least 6 transcripts of SNCA are present, including full-length 140aa protein, 126aa protein, 112aa protein, 98aa protein, 67aa protein, and 115aa protein). The SNCA gene includes 6 exons with an initiation codon in exon 2. This document provides transgenes for integration into SNCA genes. The transgene may include an RNAi cassette targeting exon 1 or exon 2 of SNCA, a promoter, a partial coding sequence encoding a peptide produced by exon 2 of SNCA (wherein the partial coding sequence is resistant to silencing by the RNAi cassette), and a splice donor.
In one embodiment, the methods provided herein describe the delivery of a transgene having a complete functional anti-silencing coding sequence and an RNAi silencing sequence (fig. 9). Functional coding sequences can include a promoter, a nucleic acid sequence for producing an RNA or protein product, and a terminator. The nucleic acid sequence can be tailored to avoid silencing by the silencing sequence (fig. 9). In one embodiment, the transgene may include a silencing sequence that targets the 5' UTR of the transcript. Functional coding sequences within a transgene may include coding sequences of a silenced gene (WT or codon-modulated) as well as alternative 5 'UTRs or no 5' UTRs not derived from the target gene. In another embodiment, the transgene may include a silencing sequence that targets the 3' UTR of the transcript. Functional coding sequences within a transgene may include coding sequences of a silenced gene (WT or codon-modulated) as well as alternative 3 'UTRs or no 3' UTRs not derived from the target gene. In yet another embodiment, the transgene may include a silencing sequence that targets the coding sequence of the gene. A functional coding sequence can include a coding sequence of a silenced gene, wherein the entire coding sequence or a portion of the coding sequence is modified to avoid silencing by the silenced sequence. Modification may be achieved by methods such as codon optimisation/tuning or by deletion of the target region. In one embodiment, a transgene described herein comprising a silencing sequence and a functional coding sequence can be transiently delivered to a cell (e.g., via a viral vector or plasmid DNA), or the transgene can be integrated into the genome of the cell. In some embodiments, a transgene may be delivered to a cell that includes one or more genes with gain-of-function mutations (fig. 7). Examples of diseases with gain-of-function mutations include: HD (Huntington's disease), SBMA (spinal bulbar muscular atrophy), SCA1 (spinocerebellar ataxia type 1), SCA2 (spinocerebellar ataxia type 2), SCA3 (spinocerebellar ataxia type 3 or Machado-Joseph disease), SCA6 (spinocerebellar ataxia type 6), SCA7 (spinocerebellar ataxia type 7), fragile X syndrome, fragile XE mental retardation, Friedrich's ataxia, myotonic dystrophy type 1, myotonic dystrophy type 2, spinocerebellar ataxia type 8, spinocerebellar ataxia type 12, spinal and bulbar muscular atrophy, JPH3, Amyotrophic Lateral Sclerosis (ALS), hereditary motor and sensory neuropathy type IIC, postsynaptic slow channel congenital myasthenia gravis syndrome, PRPS1 hyperactivity, parkinson's disease, tubular aggregative myopathy, achondroplasia, lubs X-linked mental retardation syndrome, and autosomal dominant retinitis pigmentosa.
In certain embodiments, transgenes described herein that include a silencing sequence and a functional coding sequence can be used to correct a gain-of-function disorder by silencing a particular gene and replacing expression of the gene. The gene may comprise SOD1, TRPV4, CHRNA1, CHRND, CHRNE, CHRNB1, PRPS1, LRRK2, STIM1, FGFR3, MECP2, SNCA, ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7, TBP, HTT, AR, FXN, DMPK, PABPN1, ATXN8, RHO and C9orf 72.
Transgenes described herein, including silencing sequences and functional coding sequences, can be delivered to cells using viral (e.g., AAV vectors) or non-viral methods. In certain embodiments, the AAV vectors described herein may be derived from any AAV. In certain embodiments, the AAV vector is derived from a defective and non-pathogenic parvovirus adeno-associated type 2 virus. All such vectors are derived from plasmids retaining only AAV 145bp inverted terminal repeats flanking the transgene expression cassette. Efficient gene transfer and stable transgene delivery are key features of this vector system due to integration into the genome of the transduced cell. (Wagner et al, Lancet (Lancet) 351: 91171702- & lt 3 & gt, 1998; Kearns et al, Gene therapy (Gene Ther.) 9:748- & lt 55, 1996). Other AAV serotypes including AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, and aavrh.10 as well as any novel AAV serotype can also be used in accordance with the present invention. In some embodiments, a chimeric AAV is used in which the viral origin of the Long Terminal Repeat (LTR) sequences of the viral nucleic acid is heterologous to the viral origin of the capsid sequences. Non-limiting examples include chimeric viruses with LTRs derived from AAV2 and capsids derived from AAV5, AAV6, AAV8, or AAV9 (i.e., AAV2/5, AAV2/6, AAV2/8, and AAV2/9, respectively).
The constructs described herein may also be incorporated into adenoviral vector systems. Adenovirus-based vectors are capable of very high transduction efficiency in many cell types and do not require cell division. Using such vectors, high titers and high expression levels can be obtained.
The methods and compositions described herein are applicable to any eukaryotic organism in which it is desirable to alter the organism by genomic modification. Eukaryotes include plants, algae, animals, fungi, and protists. Eukaryotes can also include plant cells, algal cells, animal cells, fungal cells, and protist cells.
Exemplary mammalian cells include, but are not limited to, oocytes, K562 cells, CHO (Chinese hamster ovary) cells, HEP-G2 cells, BaF-3 cells, Schneider cells (Schneider cells), COS cells (monkey kidney cells expressing SV 40T-antigen), CV-1 cells, HuTu80 cells, NTERA2 cells, NB4 cells, HL-60 cells, and HeLa cells, 293 cells (see, e.g., Graham et al (1977) J.Gen.Virol., 36:59), and myeloma cells such as SP 2or NS0 (see, e.g., Galfre and Milstein (1981) methods of enzymology (meth.Enzymol.) 73(B): 346) Hematopoietic stem cells, hepatic stem cells, skin stem cells, and neuronal stem cells.
The methods and compositions of the invention can be used to produce modified organisms. The modified organism may be a small mammal, a companion animal, livestock, and a primate. Non-limiting examples of rodents may include mice, rats, hamsters, gerbils, and guinea pigs. Non-limiting examples of companion animals may include cats, dogs, rabbits, hedgehog, and ferrets. Non-limiting examples of livestock may include horses, goats, sheep, pigs, llamas, alpacas, and cattle. Non-limiting examples of primates can include caput monkeys, chimpanzees, lemurs, macaques, marmosets, tamarins, spider monkeys, squirrel monkeys, and black-tailed monkeys. The methods and compositions of the invention may be used in humans.
Exemplary plants and plant cells that can be modified using the methods described herein include, but are not limited to, monocots (e.g., wheat, corn, rice, millet, barley, sugarcane), dicots (e.g., soybean, potato, tomato, alfalfa), fruit crops (e.g., tomato, apple, pear, strawberry, orange), forage crops (e.g., alfalfa), root vegetable crops (e.g., carrot, potato, beet, yam), leafy vegetable crops (e.g., lettuce, spinach); vegetative crops for consumption (e.g., soybeans and other legumes, squash, pepper, eggplant, celery, etc.), flowering plants (e.g., petunia, rose, chrysanthemum), conifers, and pine trees (e.g., fir, spruce); poplar (e.g., populus tremuloides x populus alba (p. tremula x p. alba)); fiber crops (cotton, jute, flax, bamboo), plants for phytoremediation (e.g., heavy metal accumulating plants); oil crops (e.g., sunflower, rapeseed) and plants used for experimental purposes (e.g., arabidopsis). The methods disclosed herein may be used in asparagus, oats, brassica, citrus, watermelon, capsicum, squash, carrot, erigeron, glycine, cotton, barley, lettuce, ryegrass, tomato, apple, cassava, tobacco, orychophramus, rice, alligator, phaseolus, pea, pear, plum, radish, rye, solanum, sorghum, wheat, grape, cowpea, and maize. The term plant cell encompasses isolated plant cells as well as whole plants or parts of whole plants, such as seeds, callus, leaves and roots. The present disclosure also encompasses seeds of the above plants, wherein the seeds have been modified using the compositions and/or methods described herein. The present disclosure also encompasses progeny, clones, cell lines or cells of the above transgenic plants, wherein the progeny, clones, cell lines or cells have the transgene or gene construct. Exemplary algal species include microalgae, diatoms, botryococcus braunii, chlorella vulgaris, dunaliella salina, gracilaria (gracilaria), chrysotile brevicaulis (pleurochrysis carperee), gulfweed (Sorgassum), and ulva lactuca.
The methods described in this document can comprise the use of rare-cutting endonucleases to stimulate homologous recombination or non-homologous integration of a transgenic molecule into an endogenous gene. The rare-cutting endonuclease can comprise a CRISPR, TALEN, or Zinc Finger Nuclease (ZFN). The CRISPR system may comprise CRISPR/Cas 9or CRISPR/Cas12a (Cpf 1). The CRISPR system may comprise variants that exhibit binding or cleavage activity on targets of broad PAM function (Hu et al, Nature 556,57-63,2018; Nishimasu et al, science DOI 10.1126,2018) or higher (Kleinstever et al, Nature 529:490-495,2016). The gene editing reagent may be in the form of: nucleases (Mali et al, science 339:823-826, 2013; Christian et al, Genetics (Genetics) 186: 757-.
The methods and compositions described in this document can be used in situations where it is desirable to modify the 5' end of an endogenous gene coding sequence. For example, patients with SCA2 have an extended CAG repeat sequence in exon 1. Patients with SCA2 may benefit from exon 1 replacement. In other examples, patients with a genetic disorder resulting from a loss of a functional mutation within the 5' end of an endogenous gene may benefit from replacement of the first exon of the gene.
Further, the methods and compositions described in this document can be used in situations where it is desirable to treat an gain-of-function genetic disorder while ensuring that the wild-type protein is still produced. For example, patients with retinitis pigmentosa with gain-of-function mutations in the RHO gene may benefit from a therapy that includes a transgene capable of silencing the endogenous RHO gene while simultaneously producing a wild-type RHO protein. Additional benefits of this approach include the ability to select silent target sites that are not centered on the gain-of-function mutation site. This benefit enables the design of potent silencing constructs (e.g., low off-target and high efficiency on-target) and the design of monotherapies for patients with gain-of-function mutations in different regions of the RHO gene. Further, the methods may be particularly useful in gain of function disorders associated with genes having a number of isoforms produced, including parkinson's and SNCA. Cells with gain-of-function mutations in the 5' end of the SNCA gene can benefit from the integration of a transgene comprising an RNAi cassette targeting exon 2, as well as a promoter and a portion of the coding sequence that is resistant to RNAi silencing.
The invention will be further described in the following examples, which do not limit the scope of the invention described in the claims.
Examples of the invention
Example 1: targeted integration of DNA into the ATXN2 gene
Three plasmids were constructed with a transgene in the ATXN2 gene designed to integrate into human cells. All transgenes were designed to integrate within intron 2 of the ATXN2 gene, and all were designed to insert a bidirectional partial coding sequence with a single promoter. The partial coding sequence encodes a peptide produced by exon 1 of the ATXN2 gene. The first plasmid, designated pBA1141, included left and right homology arms with sequences homologous to the starting sequence of intron 1 (i.e., successful gene targeting would result in the insertion of a cargo into pBA1141 of intron 1). From 5 'to 3', between the homologous arms, the splice donor in the reverse complement orientation, the partial coding sequence 1 with codon modulation in the reverse complement orientation (encoding the peptide produced by exon 1 of the ATXN2 gene), the EF1 α promoter in the reverse complement orientation, the CMV promoter, the partial coding sequence 2 with codon modulation (encoding the peptide produced by exon 1 of the ATXN2 gene) and the splice donor are comprised. The sequence of the pBA1141 transgene is shown in SEQ ID NO:15 (FIG. 6). Two nucleases were designed to promote integration of pBA1141 into the genome: cas9 with a (TGTGCAGGAGGGCCTGTTGGGGG; SEQ ID NO:16) target site and Cas12a with a (TTTCCCTTGTGCCTCAAGTCCATCCGT; SEQ ID NO:17) target site. The target site is also contained in pBA1141 to facilitate release of the donor molecule from the plasmid. 18-24 show the individual components within pBA 1141. 18 is the sequence of the target site including Cas9 and Cas12 a. SEQ ID NO 19 includes the sequence of the left homology arm. SEQ ID NO 20 includes the reverse complement, codon-adjusted partial coding sequence (exon 1) of the nonpathogenic ATXN2 gene. SEQ ID NO 21 includes the reverse complement EF1 alpha promoter. SEQ ID NO 22 includes the reverse complement CMV promoter. SEQ ID NO. 23 includes the codon-regulated partial coding sequence (exon 1) of the nonpathogenic ATXN2 gene. SEQ ID NO 24 includes the sequence of the right homology arm. The second plasmid, designated pBA1142, included the same cargo as pBA1135, however the homology arms were removed. Nuclease target sites are maintained to facilitate release of the transgene from the plasmid. Successful cleavage of the plasmid is expected to release the transgene, enabling the sequence to be used for integration into the ATXN2 gene by NHEJ. The sequence of pBA1141 is shown in SEQ ID NO 25. The third plasmid, designated pBA1143, included the same sequence as pBA1141, except that the sequence carrying the nuclease target site (upstream of the left homology arm) was removed and the right homology arm was shortened to 600 bp.
HEK293T cells were used for transfection. HEK293T cells were maintained at 37 ℃ and 5% CO2 in high DMEM supplemented with 10% Fetal Bovine Serum (FBS). HEK293T cells were transfected with 2ug of donor, 2ug of guide RNA (RNA form) and 2ug of Cas9(RNA form) or 2ug of Cas12a plasmid (DNA form). Transfection was performed using electroporation. Genomic DNA was isolated 72 hours post transfection and evaluated for integration events. A list of primers used to detect integration or genomic DNA is shown in table 1.
Table 1: primers for detecting integration of the transgene in ATXN 2.
Figure BDA0003097458300000471
To detect the integration of pBA1141, pBA1142 and pBA1143, PCR was performed on the genomic DNA. With respect to pBA1143, the transgene was designed to integrate precisely by HR. Thus, bands were detected in both Cas9 and Cas12a transfected samples in 3' junction PCR, indicating precise insertion into intron 1 (lanes 7-10 of fig. 17). The expected band sizes are 1,225bp (lanes 7 and 9) and 1,407bp (lanes 8 and 10). Primers oNJB201+ oNJB190 and oNJB202+ oNJB191 were used in the 3' junction PCR. With respect to pBA1142, since no homology arms are present, it is predicted that the transgene will be inserted by NHEJ insertion. Integration by NHEJ in samples transfected with Cas9 can be seen in lane 6 of fig. 17. The expected band size is 813 bp. Primers oNJB202+ oNJB211 were used in the NHEJ-insert 3' junction PCR. With respect to pBA1141, both homology arms and nuclease cleavage sites were present on the transgene (FIG. 7). Integration by HR was observed in lanes 2-4 of figure 17 and integration by NHEJ was observed in lane 5 of figure 17. The expected size of the PCR used to detect the insertion by HR was 1594bp (lane 2; primer oNJB201+ oNJB190), 1775bp (lane 3; primer oNJB202+ oNJB191), 1775bp (lane 4; primer oNJB202+ oNJB 191). The expected size of the PCR used to detect the insertion by NHEJ was 2067bp (lane 5; primers oNJB202+ oNJB 211).
The results indicate that the described transgene comprising a coding sequence with a promoter in the bidirectional part can be integrated into genomic DNA by a number of different repair pathways.
HEK293T cells were used for transfection. HEK293T cells were maintained at 37 ℃ and 5% CO2 in high DMEM supplemented with 10% Fetal Bovine Serum (FBS). HEK293T cells were transfected with 2ug of donor, 2ug of guide RNA (RNA form) and 2ug of Cas9(RNA form) or 2ug of Cas12a plasmid (DNA form). Transfection was performed using electroporation. Isolation of single cell clones including integration and extraction of RNA. RNA sequencing can be used to detect new transcripts.
Example 2: silencing of endogenous SOD1 Gene expression and expression of alternative SOD1 protein
This document describes methods for using RNAi, anti-RNAi coding sequences, and gene editing to silence and replace endogenous gene expression. These methods are particularly useful for gain-of-function disorders, including amyotrophic lateral sclerosis, in which there is a mutation in the SOD1 gene.
To verify gene silencing and replacement, the transgene was designed with an rnai (shrna) cassette targeting sequences within exon 2 of SOD 1. The shRNA includes sequence GGCCTGCATGGATTCCATGTTCAAGAGACATGGAATCCATGCAGGCC (SEQ ID NO:49), which is placed downstream of the U6 promoter. The transgene also includes the SOD1 coding sequence downstream of the CMV promoter. The sequence within the coding sequence was modified to avoid shRNA silencing. The sequence of the transgene (designated pBA1148) is shown in SEQ ID NO 10. A control vector comprising a scrambled shRNA (designated pBA 1147; SEQ ID NO:53) and WT SOD1 coding sequence (designated pBA 1149; SEQ ID NO:54) was generated.
HEK293T cells were used for transfection. HEK293T cells were maintained at 37 ℃ and 5% CO2 in high DMEM supplemented with 10% Fetal Bovine Serum (FBS). HEK293T cells were transfected with 2ug of plasmid. Transfection was performed using electroporation. RNA was isolated 48 hours post transfection and levels of SOD1 mRNA were assessed.
To use gene editing to silence SOD1 gene expression and produce an alternative SOD1 protein, two vectors were designed to be integrated into intron 1. The first vector includes, from 5 'to 3', the left homology arm, the splice acceptor, part of the coding sequence for SOD1 encoding the peptide produced by exons 2-5 (and also including mutations to avoid silencing by the RNAi cassette), a terminator, an RNAi cassette having the shRNA sequence shown in SEQ ID NO:49, and the right homology arm. The second vector includes, from 5 'to 3', a nuclease target site, a splice acceptor, a partial coding sequence of SOD1 encoding a peptide produced by exons 2-5 (and also including mutations to avoid silencing by the RNAi cassette), a terminator, an RNAi cassette having the shRNA sequence shown in SEQ ID NO:49, a second terminator in reverse complement orientation, a second partial coding sequence of SOD1 in reverse complement orientation encoding a peptide produced by exons 2-5 (and also including mutations to avoid silencing by the RNAi cassette), a second splice acceptor in reverse complement orientation, and a second nuclease target site (fig. 12).
Two additional vectors were designed to integrate into intron 3 of the SOD1 gene. The first vector comprises, from 5 'to 3', the left homology arm, the RNAi cassette having the shRNA sequence shown in SEQ ID NO:49, a promoter, part of the coding sequence of SOD1 encoding the peptide produced by exons 1 and 2 (and also including mutations to avoid silencing by the RNAi cassette), a splice donor and the right homology arm. The second vector includes, from 5 'to 3', a nuclease target site, a splice donor in reverse complement orientation, a partial coding sequence of SOD1 in reverse complement orientation that encodes peptides produced by exons 1 and 2 (and also includes mutations to avoid silencing by the RNAi cassette), a promoter in reverse complement orientation, an RNAi cassette having the shRNA sequence shown in SEQ ID NO:49, a second promoter, a second coding sequence of SOD1 that encodes peptides produced by exons 1 and 2 (and also includes mutations to avoid silencing by the RNAi cassette), a splice donor, and a second nuclease target site (fig. 16).
HEK293T cells were used for transfection. HEK293T cells were maintained at 37 ℃ and 5% CO2 in high DMEM supplemented with 10% Fetal Bovine Serum (FBS). HEK293T cells were transfected with 2ug of plasmid, 2ug of guide RNA (RNA form) and 2ug of Cas9(RNA form). Transfection was performed using electroporation. DNA was isolated 72 hours post transfection and transgene integration was assessed. Clones that included the integration event were isolated and evaluated for their SOD1 mRNA levels (both from the endogenous gene and from the modified gene).
Example 3: silencing of endogenous SNCA gene expression and expression of two SNCA protein isoforms
Mutations in SNCA have been found to cause parkinson's disease. The methods described herein can be used to correct SNCA gene expression. In some cases, SNCA is repeated or repeated three times, resulting in overproduction of a-synuclein. In other cases, mutations such as Ala30Pro will cause misfolding of the protein. Described herein is a method of reducing the expression of endogenous SNCA expression (from gene duplication and intragenic mutations) while replacing the expression of SNCA with some or all of the SNCA isoforms (at least 6 transcripts of SNCA are present, including full-length 140aa protein, 126aa protein, 112aa protein, 98aa protein, 67aa protein, and 115aa protein).
The transgene was designed to carry shRNA to silence endogenous SNCA gene expression. The transgene is also designed to replace the two SNCA protein isoforms by encoding two open reading frames, one for each isoform. The shRNA includes a 19nt hairpin sequence targeting the 3' end of the SNCA coding sequence (GGTATCAAGACTACGAAC; SEQ ID NO: 11). The two SNCA open reading frames within the transgene are designed to carry mutations at shRNA target sites. SEQ ID NO 12 shows the nucleic acid sequence of the transgene cloned into an expression plasmid (designated pBA 1153). Two other transgenes were constructed: one transgene has shRNA and two wild-type SNCA isoforms (without mutations that prevent shRNA silencing), and a second transgene has a scrambled shRNA and two SNCA isoforms with mutations.
The transgene was transfected into HEK293 cells. HEK293 cells were maintained at 37 ℃ and 5% CO2 in DMEM high glucose supplemented with 10% Fetal Bovine Serum (FBS) and 1% penicillin-streptomycin (PS) solution 100X without L-glutamine, sodium pyruvate media. HEK293 cells were transfected with each plasmid construct and combinations thereof using Lipofectamine 3000. RNA was extracted 48 hours post transfection and SNCA transcript levels were assessed. A decrease in expression of endogenous SNCA RNA and expression of RNA from the codon-regulated SNCA sequence is indicative of the functionality of the transgene.
To use gene editing to silence SNCA gene expression and produce alternative SNCA proteins while maintaining isoform production, two vectors are designed to integrate into the exon 2 intron 2 junction. The first vector includes, from 5 'to 3', the left homology arm, an RNAi cassette with shRNA sequences targeting exon 2 transcript sequences, a promoter (including a1,000 bp endogenous SNCA promoter), a partial coding sequence encoding the start codon and peptides produced by exon 2 of the endogenous SNCA gene (and also including mutations to avoid silencing by the RNAi cassette), a splice donor and the right homology arm. The splice donor and the right homologous arm are sequences starting from the 5' end of the endogenous intron 2. The second vector includes, from 5 'to 3', a nuclease target site, a splice donor in an inverse complement orientation, a partial coding sequence of SNCA in an inverse complement orientation that encodes a peptide produced by exon 2 (and also includes mutations to avoid silencing by the RNAi cassette), a promoter in an inverse complement orientation, an RNAi cassette with an shRNA targeting exon 2, a second promoter, a second partial coding sequence of SNCA that encodes a peptide produced by exon 2 (and also includes mutations to avoid silencing by the RNAi cassette), a splice donor, and a second nuclease target site (fig. 16). The splice donor sequence is the splice donor sequence from intron 2 of the SNCA gene. The nuclease is designed to facilitate integration of the transgene into the exon 2 intron 2 junction.
The transgene and nuclease were transfected into HEK293 cells. HEK293 cells were maintained at 37 ℃ and 5% CO2 in DMEM high glucose supplemented with 10% Fetal Bovine Serum (FBS) and 1% penicillin-streptomycin (PS) solution 100X without L-glutamine, sodium pyruvate media. HEK293 cells were transfected with each plasmid construct and combinations thereof using Lipofectamine 3000. Clones containing the integration event were isolated and RNA was extracted. A decrease in expression of the endogenous SNCA RNA, as well as expression of RNA from the modified SNCA gene, is indicative of the functionality of the transgene.
Example 4: silencing of endogenous RHO gene expression and expression of surrogate RHO proteins
The transgene was designed to carry shRNA for silencing expression of endogenous RHO genes and an open reading frame encoding a wild-type RHO protein. The RHO protein sequence is shown in SEQ ID NO 13. The silencing sequence carries a hairpin sequence that targets the endogenous RHO transcript. The RHO open reading frame within the transgene is codon adjusted to include minimal sequence homology at the shRNA target site.
The transgene was transfected into HEK293 cells. HEK293 cells were maintained at 37 ℃ and 5% CO2 in DMEM high glucose supplemented with 10% Fetal Bovine Serum (FBS) and 1% penicillin-streptomycin (PS) solution 100X without L-glutamine, sodium pyruvate media. HEK293 cells were transfected with each plasmid construct and combinations thereof using Lipofectamine 3000. Three days after transfection, RNA was extracted from the cells and transcript levels thereof were evaluated. Reduced expression of endogenous RHO RNA as well as expression of RNA from the codon-regulated RHO sequence is indicative of the functionality of the transgene.
Example 5: silencing of endogenous C9orf72 Gene expression and expression of replacement C9orf72 protein
The transgene was designed to carry shRNA for silencing expression of the endogenous C9orf72 gene and an open reading frame encoding the wild-type C9orf72 protein. The C9orf72 protein sequence is shown in SEQ ID NO: 14. The silencing sequence carries a hairpin sequence that targets the endogenous C9orf72 transcript. The C9orf72 open reading frame within the transgene was codon adjusted to include minimal sequence homology at the shRNA target site.
The transgene was transfected into HEK293 cells. HEK293 cells were maintained at 37 ℃ and 5% CO2 in DMEM high glucose supplemented with 10% Fetal Bovine Serum (FBS) and 1% penicillin-streptomycin (PS) solution 100X without L-glutamine, sodium pyruvate media. HEK293 cells were transfected with each plasmid construct and combinations thereof using Lipofectamine 3000. Three days after transfection, RNA was extracted from the cells and transcript levels thereof were evaluated. Reduced expression of endogenous C9orf72 RNA and expression of codon-regulated C9orf72 sequences are indicative of transgene functionality.
Example 6: targeted integration of DNA into the ATXN2 gene
A transgene targeting ATXN2 was designed to replace the 5' end of the ATXN2 coding sequence. A plasmid designated pBA1012-D1 was constructed with a transgene designed to integrate the WT coding sequence into Intron 1 of the ATXN2 gene (FIG. 4). The transgene includes a first homology arm homologous to the sequence following the splice donor site in intron 1 (SEQ ID NO: 2). Adjacent to the first homology arm is the target site for Cas9 nuclease. The first homology arm is followed by the reverse complement splice donor sequence of the ATXN2 gene and exon 1 (unexpanded CAG repeats; SEQ ID NO: 3). Following the first coding sequence is the EF1 alpha promoter (SEQ ID NO: 4). There is a second set of functional elements in the head joint orientation. The beginning of the second set of elements included the CMV promoter (SEQ ID NO:5) driving expression of the codon-regulated exon 1 coding sequence (SEQ ID NO:6) of the ATXN2 gene. The coding sequence is followed by a splice donor site and a second homology arm. The second homology arm includes the rare-cutting endonuclease target site (SEQ ID NO: 8). The transgene sequence is shown in SEQ ID NO 1.
The corresponding Cas9 nuclease was designed to generate three double strand breaks: 1) within intron 1 of the endogenous ATXN2 gene, 2) adjacent to the first homology arm of the pBA1012-D1 transgene, and 3) within the second homology arm of the pBA1012-D1 transgene. The target sequence for Cas9 nuclease is shown in SEQ ID No. 8.
Confirmation of the function of the transgene and CRISPR vector was achieved by transfection of HEK293 cells. HEK293 cells were maintained at 37 ℃ and 5% CO2 in DMEM high glucose supplemented with 10% Fetal Bovine Serum (FBS) and 1% penicillin-streptomycin (PS) solution 100X without L-glutamine, sodium pyruvate media. HEK293 cells were transfected with each plasmid construct and combinations thereof using Lipofectamine 3000. Two days after transfection, DNA was extracted and evaluated for mutations and targeted insertions within the ATXN2 gene. Nuclease activity was analyzed using Cel-I analysis or by deep sequencing of amplicons comprising CRISPR/Cas9 target sequences. Successful integration of the transgene was analyzed using PCR.
OTHER EMBODIMENTS
It is to be understood that while the invention has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims.
Sequence listing
<110> blue allele Limited liability company
<120> methods for altering gene expression of genetic disorders
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<150> 62/754,548
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<151> 2018-11-05
<150> 62/756,175
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gctggaccca ggctggaccc tggggggaca tctctggagg ggagaagtta gggccgcgtc 60
ccccgtgccg gttaaagggg taggcaccgg gctcctccgg aatcatcagg gtctgtcggg 120
gctctctccc cgccccctcc gagtcctggg aaagatcgga ggacggggtg gagacaagtg 180
ggccttggcc cccgcacccc tctgcgttcg tgtccgaggc ggcggcgggg gctcccgaac 240
tcccctgaaa tcgtggggct ccatgtggcc tccggcagcg ttccaccctc ccccacctgg 300
ggaagggaag gggtggggag tgcgtgccga cacccacctg cccaggccgg gcctcccgcc 360
gccggaggtc gccgcgacca ccgaggaggg agccgtggcc gaggacgagg agaccgagga 420
cgaggacggc gaaggcgcgg cggcgggcga cgctagaagg ccgctgccgc cgggcttgcg 480
gacattggca gccgcgggcg gcggctgctg ctgctgctgc tgctgctgct gttgctgctg 540
ctgctgctgc tgctgctgct gctgctgctg ctggggcttc agcgacatgg tgaggggccc 600
atacaccggc tcgcacgccg ggcggggaca gccgggagcc gggcgcgcca aggagacgcc 660
ggaacgcggc ggggacgcgc gggcgccgag cggggaggcg cgggttggcg cggccggagg 720
ggcgcccggg ctggcgaggg ggagaaggag gacgacgaag gggcggggag gcccgccgag 780
accaaggagc cgccgggagc cgggccgaaa cgcgccgccg ccgttgccgt tgctaccaaa 840
acagtctgag gcggagggag gcgagctctg ccgggaggga ggggggccgg ggccgggcgg 900
gggaggggcg gcggagggat acggtcccgg ggccgcgcca ccgccgcccc gcccgctccg 960
ccgcgccggc cgctggagcg agcgccaccc gggccacctg gctgcggcga agcggcgaga 1020
ctcggtggcc accgcgggac tccgaggagc tgcggccgct gagcgcattc acgacacctg 1080
aaatggaaga aaaaaacttt gaaccactgt ctgaggcttg agaatgaacc aagatccaaa 1140
ctcaaaaagg gcaaattcca aggagaatta catcaagtgc caagctggcc taacttcagt 1200
ctccacccac tcagtgtggg gaaactccat cgcataaaac ccctcccccc aacctaaaga 1260
cgacgtactc caaaagctcg agaactaatc gaggtgcctg gacggcgccc ggtactccgt 1320
ggagtcacat gaagcgacgg ctgaggacgg aaaggccctt ttcctttgtg tgggtgactc 1380
acccgcccgc tctcccgagc gccgcgtcct ccattttgag ctccctgcag cagggccggg 1440
aagcggccat ctttccgctc acgcaactgg tgccgaccgg gccagccttg ccgcccaggg 1500
cggggcgata cacggcggcg cgaggccagg caccagagca ggccggccag cttgagacta 1560
cccccgtccg attctcggtg gccgcgctcg caggccccgc ctcgccgaac atgtgcgctg 1620
ggacgcacgg gccccgtcgc cgcccgcggc cccaaaaacc gaaataccag tgtgcagatc 1680
ttggcccgca tttacaagac tatcttgcca gaaaaaaagc gtcgcagcag gtcatcaaaa 1740
attttaaatg gctagagact tatcgaaagc agcgagacag gcgcgaaggt gccaccagat 1800
tcgcacgcgg cggccccagc gcccaggcca ggcctcaact caagcacgag gcgaaggggc 1860
tccttaagcg caaggcctcg aactctccca cccacttcca acccgaagct cgggatcaag 1920
aatcacgtac tgcagccagg ggcgtggaag taattcaagg cacgcaaggg ccataacccg 1980
taaagaggcc aggcccgcgg gaaccacaca cggcacttac ctgtgttctg gcggcaaacc 2040
cgttgcgaaa aagaacgttc acggcgacta ctgcacttat atacggttct cccccaccct 2100
cgggaaaaag gcggagccag tacacgacat cactttccca gtttaccccg cgccaccttc 2160
tctaggcacc ggttcaattg ccgacccctc cccccaactt ctcggggact gtgggcgatg 2220
tgcgctctgc ccactgacgg gcaccggagc cgttacataa cttacggtaa atggcccgcc 2280
tggctgaccg cccaacgacc cccgcccatt gacgtcaata atgacgtatg ttcccatagt 2340
aacgccaata gggactttcc attgacgtca atgggtggag tatttacggt aaactgccca 2400
cttggcagta catcaagtgt atcatatgcc aagtacgccc cctattgacg tcaatgacgg 2460
taaatggccc gcctggcatt atgcccagta catgacctta tgggactttc ctacttggca 2520
gtacatctac gtattagtca tcgctattac catggtgatg cggttttggc agtacatcaa 2580
tgggcgtgga tagcggtttg actcacgggg atttccaagt ctccacccca ttgacgtcaa 2640
tgggagtttg ttttggcacc aaaatcaacg ggactttcca aaatgtcgta acaactccgc 2700
cccattgacg caaatgggcg gtaggcgtgt acggtgggag gtctatataa gcagagctat 2760
gaggagtgcg gcagctgccc ctcgcagtcc agctgttgca accgagtcta ggcgctttgc 2820
ggctgcccgc tggcccgggt ggagatccct tcaacggcca gcacgaagat cagggcgcgg 2880
aggaggagga gccgctcccg gcccttatcc cagtgctgcc ccgccccctc ccggccctgg 2940
gcctccccct agtcgccaga gtagtcctcc gtcagcaagc gactgtttcg ggtcaaacgg 3000
taatggagga ggcgccttca ggccggggtc tcgacggctc ctgggcctgg gcggacctcc 3060
tagacccttc gtagtcctcc tccttcctct ggcatctcca ggagcccccc cggccgcgcc 3120
tactagagct agtccgctgg gcgcgagggc tagccctccc agatcagggg tctcattggc 3180
acgaccagca cctggttgtc cgagacccgc ctgcgaacct gtgtatggcc cactgacgat 3240
gagcttgaaa ccgcaacagc agcaacaaca gcaacagcaa cagcagcagc aacaacaaca 3300
gcagcagcaa cagcaacagc aacccccacc ggcggccgcg aacgttcgga aaccaggggg 3360
gtccggactc ttggcttccc ccgctgcggc tccttcacct tccagtagct cagtcagctc 3420
atccagcgcg acggcaccat ccagcgttgt agctgccaca tccggcggtg ggagaccagg 3480
gctgggcagg tgggtgtcgg cacctccggc gcgcgggtgg tggccgatcc gcattgctgt 3540
tcgaggccgc agtggagaag gcgcctgtgg aacatcggtg ggtgagggct ggacccaggc 3600
tggaccctgg agatccgggg tggcggtgct ggtggcaggg ggcgggcacc ctgcgcactt 3660
atcccaaccc ccgccccaat ttcggaaatg ctaggagaga gagattgcag caggggacgt 3720
ggtcgggttc ctgaaggcag aaaggcgggt gtttactagc gtctttttcc ctcctaagcc 3780
ggggttgtag taggggctgg ggg 3803
<210> 2
<211> 300
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> left homology arm
<400> 2
ggggacatct ctggagggga gaagttaggg ccgcgtcccc cgtgccggtt aaaggggtag 60
gcaccgggct cctccggaat catcagggtc tgtcggggct ctctccccgc cccctccgag 120
tcctgggaaa gatcggagga cggggtggag acaagtgggc cttggccccc gcacccctct 180
gcgttcgtgt ccgaggcggc ggcgggggct cccgaactcc cctgaaatcg tggggctcca 240
tgtggcctcc ggcagcgttc caccctcccc cacctgggga agggaagggg tggggagtgc 300
<210> 3
<211> 731
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> partial code sequence
<400> 3
ctgcccaggc cgggcctccc gccgccggag gtcgccgcga ccaccgagga gggagccgtg 60
gccgaggacg aggagaccga ggacgaggac ggcgaaggcg cggcggcggg cgacgctaga 120
aggccgctgc cgccgggctt gcggacattg gcagccgcgg gcggcggctg ctgctgctgc 180
tgctgctgct gctgttgctg ctgctgctgc tgctgctgct gctgctgctg ctgctggggc 240
ttcagcgaca tggtgagggg cccatacacc ggctcgcacg ccgggcgggg acagccggga 300
gccgggcgcg ccaaggagac gccggaacgc ggcggggacg cgcgggcgcc gagcggggag 360
gcgcgggttg gcgcggccgg aggggcgccc gggctggcga gggggagaag gaggacgacg 420
aaggggcggg gaggcccgcc gagaccaagg agccgccggg agccgggccg aaacgcgccg 480
ccgccgttgc cgttgctacc aaaacagtct gaggcggagg gaggcgagct ctgccgggag 540
ggaggggggc cggggccggg cgggggaggg gcggcggagg gatacggtcc cggggccgcg 600
ccaccgccgc cccgcccgct ccgccgcgcc ggccgctgga gcgagcgcca cccgggccac 660
ctggctgcgg cgaagcggcg agactcggtg gccaccgcgg gactccgagg agctgcggcc 720
gctgagcgca t 731
<210> 4
<211> 1182
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> promoter
<400> 4
tcacgacacc tgaaatggaa gaaaaaaact ttgaaccact gtctgaggct tgagaatgaa 60
ccaagatcca aactcaaaaa gggcaaattc caaggagaat tacatcaagt gccaagctgg 120
cctaacttca gtctccaccc actcagtgtg gggaaactcc atcgcataaa acccctcccc 180
ccaacctaaa gacgacgtac tccaaaagct cgagaactaa tcgaggtgcc tggacggcgc 240
ccggtactcc gtggagtcac atgaagcgac ggctgaggac ggaaaggccc ttttcctttg 300
tgtgggtgac tcacccgccc gctctcccga gcgccgcgtc ctccattttg agctccctgc 360
agcagggccg ggaagcggcc atctttccgc tcacgcaact ggtgccgacc gggccagcct 420
tgccgcccag ggcggggcga tacacggcgg cgcgaggcca ggcaccagag caggccggcc 480
agcttgagac tacccccgtc cgattctcgg tggccgcgct cgcaggcccc gcctcgccga 540
acatgtgcgc tgggacgcac gggccccgtc gccgcccgcg gccccaaaaa ccgaaatacc 600
agtgtgcaga tcttggcccg catttacaag actatcttgc cagaaaaaaa gcgtcgcagc 660
aggtcatcaa aaattttaaa tggctagaga cttatcgaaa gcagcgagac aggcgcgaag 720
gtgccaccag attcgcacgc ggcggcccca gcgcccaggc caggcctcaa ctcaagcacg 780
aggcgaaggg gctccttaag cgcaaggcct cgaactctcc cacccacttc caacccgaag 840
ctcgggatca agaatcacgt actgcagcca ggggcgtgga agtaattcaa ggcacgcaag 900
ggccataacc cgtaaagagg ccaggcccgc gggaaccaca cacggcactt acctgtgttc 960
tggcggcaaa cccgttgcga aaaagaacgt tcacggcgac tactgcactt atatacggtt 1020
ctcccccacc ctcgggaaaa aggcggagcc agtacacgac atcactttcc cagtttaccc 1080
cgcgccacct tctctaggca ccggttcaat tgccgacccc tccccccaac ttctcgggga 1140
ctgtgggcga tgtgcgctct gcccactgac gggcaccgga gc 1182
<210> 5
<211> 508
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> promoter
<400> 5
cgttacataa cttacggtaa atggcccgcc tggctgaccg cccaacgacc cccgcccatt 60
gacgtcaata atgacgtatg ttcccatagt aacgccaata gggactttcc attgacgtca 120
atgggtggag tatttacggt aaactgccca cttggcagta catcaagtgt atcatatgcc 180
aagtacgccc cctattgacg tcaatgacgg taaatggccc gcctggcatt atgcccagta 240
catgacctta tgggactttc ctacttggca gtacatctac gtattagtca tcgctattac 300
catggtgatg cggttttggc agtacatcaa tgggcgtgga tagcggtttg actcacgggg 360
atttccaagt ctccacccca ttgacgtcaa tgggagtttg ttttggcacc aaaatcaacg 420
ggactttcca aaatgtcgta acaactccgc cccattgacg caaatgggcg gtaggcgtgt 480
acggtgggag gtctatataa gcagagct 508
<210> 6
<211> 731
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> partial code sequence
<400> 6
atgaggagtg cggcagctgc ccctcgcagt ccagctgttg caaccgagtc taggcgcttt 60
gcggctgccc gctggcccgg gtggagatcc cttcaacggc cagcacgaag atcagggcgc 120
ggaggaggag gagccgctcc cggcccttat cccagtgctg ccccgccccc tcccggccct 180
gggcctcccc ctagtcgcca gagtagtcct ccgtcagcaa gcgactgttt cgggtcaaac 240
ggtaatggag gaggcgcctt caggccgggg tctcgacggc tcctgggcct gggcggacct 300
cctagaccct tcgtagtcct cctccttcct ctggcatctc caggagcccc cccggccgcg 360
cctactagag ctagtccgct gggcgcgagg gctagccctc ccagatcagg ggtctcattg 420
gcacgaccag cacctggttg tccgagaccc gcctgcgaac ctgtgtatgg cccactgacg 480
atgagcttga aaccgcaaca gcagcaacaa cagcaacagc aacagcagca gcaacaacaa 540
cagcagcagc aacagcaaca gcaaccccca ccggcggccg cgaacgttcg gaaaccaggg 600
gggtccggac tcttggcttc ccccgctgcg gctccttcac cttccagtag ctcagtcagc 660
tcatccagcg cgacggcacc atccagcgtt gtagctgcca catccggcgg tgggagacca 720
gggctgggca g 731
<210> 7
<211> 300
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> Right homology arm
<400> 7
ctccggcgcg cgggtggtgg ccgatccgca ttgctgttcg aggccgcagt ggagaaggcg 60
cctgtggaac atcggtgggt gagggctgga cccaggctgg accctggaga tccggggtgg 120
cggtgctggt ggcagggggc gggcaccctg cgcacttatc ccaacccccg ccccaatttc 180
ggaaatgcta ggagagagag attgcagcag gggacgtggt cgggttcctg aaggcagaaa 240
ggcgggtgtt tactagcgtc tttttccctc ctaagccggg gttgtagtag gggctggggg 300
<210> 8
<211> 23
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> target site
<400> 8
gctggaccca ggctggaccc tgg 23
<210> 9
<211> 19
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> shRNA targeting SOD1
<400> 9
ggcctgcatg gattccatg 19
<210> 10
<211> 1437
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> constructs
<400> 10
gaattcgcgg ccgcttctag aggtttgggg ccagagtggg cgaggcgcgg aggtctggcc 60
tataaagtag tcgcggagac ggggtgctgg tttgcgtcgt agtctcctgc agcgtctggg 120
gtttccgttg cagtcctcgg aaccaggacc tcggcgtggc ctagcgagtt gccaccatgg 180
cgacgaaggc cgtgtgcgtg ctgaagggcg acggcccagt gcagggcatc atcaatttcg 240
agcagaagga aagtaatgga ccagtgaagg tgtggggaag cattaaagga ctgactgaag 300
gtttacacgg ctttcatgtt catgagtttg gagataatac agcaggctgt accagtgcag 360
gtcctcactt taatcctcta tccagaaaac acggtgggcc aaaggatgaa gagaggcatg 420
ttggagactt gggcaatgtg actgctgaca aagatggtgt ggccgatgtg tctattgaag 480
attctgtgat ctcactctca ggagaccatt gcatcattgg ccgcacactg gtggtccatg 540
aaaaagcaga tgacttgggc aaaggtggaa atgaagaaag tacaaagaca ggaaacgctg 600
gaagtcgttt ggcttgtggt gtaattggga tcgcccaata aacattccct tggatgtagt 660
ctgaggcccc ttaactcatc tgttatcctg ctagctgtag aaatgtatcc tgataaacat 720
taaacactgt aatcttaaaa gtgtaattgt gtgacttttt cagagttgct ttaaagtacc 780
tgtagtgaga aactgattta tgatcacttg gaagatttgt atagttttat aaaactcagt 840
taaaatgtct gtttcaatga cctgtatttt gccagactta aatcacagat gggtattaaa 900
cttgtcagaa tttctttgtc attcaagcct gtgaataaaa accctgtatg gcacttatta 960
tgaggctatt aaaagaatcc aaattcaaac taaaaacttg tttattgcag cttataatgg 1020
ttacaaataa agcaatagca tcacaaattt cacaaataaa gcattttttt cactgcattc 1080
tagttgtggt ttgtccaaac tcatcaatgt atcttatcat gtctggatca agcttgaggg 1140
cctatttccc atgattcctt catatttgca tatacgatac aaggctgtta gagagataat 1200
tggaattaat ttgactgtaa acacaaagat attagtacaa aatacgtgac gtagaaagta 1260
ataatttctt gggtagtttg cagttttaaa attatgtttt aaaatggact atcatatgct 1320
taccgtaact tgaaagtatt tcgatttctt ggctttatat atcttgtgga aaggacgaaa 1380
caccggcctg catggattcc atgttcaaga gacatggaat ccatgcaggc ctttttt 1437
<210> 11
<211> 18
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> SNCA-Targeted shRNA
<400> 11
ggtatcaaga ctacgaac 18
<210> 12
<211> 1980
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> constructs
<400> 12
gccaccatgg atgtattcat gaaaggactt tcaaaggcca aggagggagt tgtggctgct 60
gctgagaaaa ccaaacaggg tgtggcagaa gcagcaggaa agacaaaaga gggtgttctc 120
tatgtaggct ccaaaaccaa ggagggagtg gtgcatggtg tggcaacagt ggctgagaag 180
accaaagagc aagtgacaaa tgttggagga gcagtggtga cgggtgtgac agcagtagcc 240
cagaagacag tggagggagc agggagcatt gcagcagcca ctggctttgt caaaaaggac 300
cagttgggca agaatgaaga aggagcccca caggaaggaa ttctggaaga tatgcctgtg 360
gatcctgaca atgaggctta tgaaatgcct tctgaggaag gctaccagga ttatgaacct 420
gaagcctaaa acttgtttat tgcagcttat aatggttaca aataaagcaa tagcatcaca 480
aatttcacaa ataaagcatt tttttcactg cattctagtt gtggtttgtc caaactcatc 540
aatgtatctt atcatgtctg gatcggggtt ggggttgcgc cttttccaag gcagccctgg 600
gtttgcgcag ggacgcggct gctctgggcg tggttccggg aaacgcagcg gcgccgaccc 660
tgggtctcgc acattcttca cgtccgttcg cagcgtcacc cggatcttcg ccgctaccct 720
tgtgggcccc ccggcgacgc ttcctgctcc gcccctaagt cgggaaggtt ccttgcggtt 780
cgcggcgtgc cggacgtgac aaacggaagc cgcacgtctc actagtaccc tcgcagacgg 840
acagcgccag ggagcaatgg cagcgcgccg accgcgatgg gctgtggcca atagcggctg 900
ctcagcaggg cgcgccgaga gcagcggccg ggaaggggcg gtgcgggagg cggggtgtgg 960
ggcggtagtg tgggccctgt tcctgcccgc gcggtgttcc gcattctgca agcctccgga 1020
gcgcacgtcg gcagtcggct ccctcgttga ccgaatcacc gacctctctc cccagctctg 1080
gctaactaga gaacccactg cttactggct tatcgaaatg ccaccatgga tgtattcatg 1140
aaaggacttt caaaggccaa ggagggagtt gtggctgctg ctgagaaaac caaacagggt 1200
gtggcagaag cagcaggaaa gacaaaagag ggtgttctct atgtaggctc caaaaccaag 1260
gagggagtgg tgcatggtgt ggcaacagtg gctgagaaga ccaaagagca agtgacaaat 1320
gttggaggag cagtggtgac gggtgtgaca gcagtagccc agaagacagt ggagggagca 1380
gggagcattg cagcagccac tggctttgtc aaaaaggacc agttgggcaa ggaaggctac 1440
caggattatg aacctgaagc ctaactgtgc cttctagttg ccagccatct gttgtttgcc 1500
cctcccccgt gccttccttg accctggaag gtgccactcc cactgtcctt tcctaataaa 1560
atgaggaaat tgcatcgcat tgtctgagta ggtgtcattc tattctgggg ggtggggtgg 1620
ggcaggacag caagggggag gattgggaag agaatagcag gcatgctggg gaaagcttga 1680
gggcctattt cccatgattc cttcatattt gcatatacga tacaaggctg ttagagagat 1740
aattggaatt aatttgactg taaacacaaa gatattagta caaaatacgt gacgtagaaa 1800
gtaataattt cttgggtagt ttgcagtttt aaaattatgt tttaaaatgg actatcatat 1860
gcttaccgta acttgaaagt atttcgattt cttggcttta tatatcttgt ggaaaggacg 1920
aaacaccggg tatcaagact acgaacttca agagagttcg tagtcttgat accctttttt 1980
<210> 13
<211> 348
<212> PRT
<213> Intelligent (Homo sapiens)
<400> 13
Met Asn Gly Thr Glu Gly Pro Asn Phe Tyr Val Pro Phe Ser Asn Ala
1 5 10 15
Thr Gly Val Val Arg Ser Pro Phe Glu Tyr Pro Gln Tyr Tyr Leu Ala
20 25 30
Glu Pro Trp Gln Phe Ser Met Leu Ala Ala Tyr Met Phe Leu Leu Ile
35 40 45
Val Leu Gly Phe Pro Ile Asn Phe Leu Thr Leu Tyr Val Thr Val Gln
50 55 60
His Lys Lys Leu Arg Thr Pro Leu Asn Tyr Ile Leu Leu Asn Leu Ala
65 70 75 80
Val Ala Asp Leu Phe Met Val Leu Gly Gly Phe Thr Ser Thr Leu Tyr
85 90 95
Thr Ser Leu His Gly Tyr Phe Val Phe Gly Pro Thr Gly Cys Asn Leu
100 105 110
Glu Gly Phe Phe Ala Thr Leu Gly Gly Glu Ile Ala Leu Trp Ser Leu
115 120 125
Val Val Leu Ala Ile Glu Arg Tyr Val Val Val Cys Lys Pro Met Ser
130 135 140
Asn Phe Arg Phe Gly Glu Asn His Ala Ile Met Gly Val Ala Phe Thr
145 150 155 160
Trp Val Met Ala Leu Ala Cys Ala Ala Pro Pro Leu Ala Gly Trp Ser
165 170 175
Arg Tyr Ile Pro Glu Gly Leu Gln Cys Ser Cys Gly Ile Asp Tyr Tyr
180 185 190
Thr Leu Lys Pro Glu Val Asn Asn Glu Ser Phe Val Ile Tyr Met Phe
195 200 205
Val Val His Phe Thr Ile Pro Met Ile Ile Ile Phe Phe Cys Tyr Gly
210 215 220
Gln Leu Val Phe Thr Val Lys Glu Ala Ala Ala Gln Gln Gln Glu Ser
225 230 235 240
Ala Thr Thr Gln Lys Ala Glu Lys Glu Val Thr Arg Met Val Ile Ile
245 250 255
Met Val Ile Ala Phe Leu Ile Cys Trp Val Pro Tyr Ala Ser Val Ala
260 265 270
Phe Tyr Ile Phe Thr His Gln Gly Ser Asn Phe Gly Pro Ile Phe Met
275 280 285
Thr Ile Pro Ala Phe Phe Ala Lys Ser Ala Ala Ile Tyr Asn Pro Val
290 295 300
Ile Tyr Ile Met Met Asn Lys Gln Phe Arg Asn Cys Met Leu Thr Thr
305 310 315 320
Ile Cys Cys Gly Lys Asn Pro Leu Gly Asp Asp Glu Ala Ser Ala Thr
325 330 335
Val Ser Lys Thr Glu Thr Ser Gln Val Ala Pro Ala
340 345
<210> 14
<211> 481
<212> PRT
<213> Intelligent (Homo sapiens)
<400> 14
Met Ser Thr Leu Cys Pro Pro Pro Ser Pro Ala Val Ala Lys Thr Glu
1 5 10 15
Ile Ala Leu Ser Gly Lys Ser Pro Leu Leu Ala Ala Thr Phe Ala Tyr
20 25 30
Trp Asp Asn Ile Leu Gly Pro Arg Val Arg His Ile Trp Ala Pro Lys
35 40 45
Thr Glu Gln Val Leu Leu Ser Asp Gly Glu Ile Thr Phe Leu Ala Asn
50 55 60
His Thr Leu Asn Gly Glu Ile Leu Arg Asn Ala Glu Ser Gly Ala Ile
65 70 75 80
Asp Val Lys Phe Phe Val Leu Ser Glu Lys Gly Val Ile Ile Val Ser
85 90 95
Leu Ile Phe Asp Gly Asn Trp Asn Gly Asp Arg Ser Thr Tyr Gly Leu
100 105 110
Ser Ile Ile Leu Pro Gln Thr Glu Leu Ser Phe Tyr Leu Pro Leu His
115 120 125
Arg Val Cys Val Asp Arg Leu Thr His Ile Ile Arg Lys Gly Arg Ile
130 135 140
Trp Met His Lys Glu Arg Gln Glu Asn Val Gln Lys Ile Ile Leu Glu
145 150 155 160
Gly Thr Glu Arg Met Glu Asp Gln Gly Gln Ser Ile Ile Pro Met Leu
165 170 175
Thr Gly Glu Val Ile Pro Val Met Glu Leu Leu Ser Ser Met Lys Ser
180 185 190
His Ser Val Pro Glu Glu Ile Asp Ile Ala Asp Thr Val Leu Asn Asp
195 200 205
Asp Asp Ile Gly Asp Ser Cys His Glu Gly Phe Leu Leu Asn Ala Ile
210 215 220
Ser Ser His Leu Gln Thr Cys Gly Cys Ser Val Val Val Gly Ser Ser
225 230 235 240
Ala Glu Lys Val Asn Lys Ile Val Arg Thr Leu Cys Leu Phe Leu Thr
245 250 255
Pro Ala Glu Arg Lys Cys Ser Arg Leu Cys Glu Ala Glu Ser Ser Phe
260 265 270
Lys Tyr Glu Ser Gly Leu Phe Val Gln Gly Leu Leu Lys Asp Ser Thr
275 280 285
Gly Ser Phe Val Leu Pro Phe Arg Gln Val Met Tyr Ala Pro Tyr Pro
290 295 300
Thr Thr His Ile Asp Val Asp Val Asn Thr Val Lys Gln Met Pro Pro
305 310 315 320
Cys His Glu His Ile Tyr Asn Gln Arg Arg Tyr Met Arg Ser Glu Leu
325 330 335
Thr Ala Phe Trp Arg Ala Thr Ser Glu Glu Asp Met Ala Gln Asp Thr
340 345 350
Ile Ile Tyr Thr Asp Glu Ser Phe Thr Pro Asp Leu Asn Ile Phe Gln
355 360 365
Asp Val Leu His Arg Asp Thr Leu Val Lys Ala Phe Leu Asp Gln Val
370 375 380
Phe Gln Leu Lys Pro Gly Leu Ser Leu Arg Ser Thr Phe Leu Ala Gln
385 390 395 400
Phe Leu Leu Val Leu His Arg Lys Ala Leu Thr Leu Ile Lys Tyr Ile
405 410 415
Glu Asp Asp Thr Gln Lys Gly Lys Lys Pro Phe Lys Ser Leu Arg Asn
420 425 430
Leu Lys Ile Asp Leu Asp Leu Thr Ala Glu Gly Asp Leu Asn Ile Ile
435 440 445
Met Ala Leu Ala Glu Lys Ile Lys Pro Gly Leu His Ser Phe Ile Phe
450 455 460
Gly Arg Pro Phe Tyr Thr Ser Val Gln Glu Arg Asp Val Leu Met Thr
465 470 475 480
Phe
<210> 15
<211> 4998
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> constructs
<400> 15
tttgtgcagg agggcctgtt gggggtgttt cccttgtgcc tcaagtccat ccgttttaag 60
gaattctgct gccttcaaag gtccagcctc ccgcagcatc cccgccccct cccccggcgg 120
tcaagatgga gggagcgggc ggcctcccct ccccacgcgt gttgggaggg gttctcgggt 180
agcggcgatg gtcagccccg gctccccctt ccgcacgatc ctccgcccgc agcgtgggga 240
tgctcgggca gctcctccac tcccggttta ggtgtgaacg ttggaggggt ctggaggctg 300
tggtggcgtt ttccggaaca tgtccccctc catgggggac atctctggag gggagaagtt 360
agggccgcgt cccccgtgcc ggttaaaggg gtaggcaccg ggctcctccg gaatcatcag 420
ggtctgtcgg ggctctctcc ccgccccctc cgagtgtgcc gacacccacc tgcccaggcc 480
gggcctcccg ccgccggagg tcgccgcgac caccgaggag ggagccgtgg ccgaggacga 540
ggagaccgag gacgaggacg gcgaaggcgc ggcggcgggc gacgctagaa ggccgctgcc 600
gccgggcttg cggacattgg cagccgcggg cggcggctgc tgctgctgct gctgctgctg 660
ctgttgctgc tgctgctgct gctgctgctg ctgctgctgc tgctggggct tcagcgacat 720
ggtgaggggc ccatacaccg gctcgcacgc cgggcgggga cagccgggag ccgggcgcgc 780
caaggagacg ccggaacgcg gcggggacgc gcgggcgccg agcggggagg cgcgtgtagg 840
agccgcggga ggtgcgcccg gggatgcgag cggaagcagc agcaccacaa atggccgggg 900
aggccctccc agccccaaca agcgtctaga cccagggcga aaagctcccc caccatttcc 960
atttgaccca aagcagtcgc tcgcggatgg gggtgaggat tgccttgagg gtgggggccc 1020
tggccccgga ggaggagggg cggcgcttgg atatggtcct ggcgcagctc ccccaccacc 1080
ccttccggat ctgcgcgctg gtcgctgcaa actcctccag ccgggccacc tggctgcggc 1140
gaacctcctt gattccgttg ccaccgcagg ggatctcggc gctgccgcag cgctccgcat 1200
ggtggcggtg gcgaccggtg gatcccgggc ccgcggtacc gtcgactgca gaattcctca 1260
cgacacctga aatggaagaa aaaaactttg aaccactgtc tgaggcttga gaatgaacca 1320
agatccaaac tcaaaaaggg caaattccaa ggagaattac atcaagtgcc aagctggcct 1380
aacttcagtc tccacccact cagtgtgggg aaactccatc gcataaaacc cctcccccca 1440
acctaaagac gacgtactcc aaaagctcga gaactaatcg aggtgcctgg acggcgcccg 1500
gtactccgtg gagtcacatg aagcgacggc tgaggacgga aaggcccttt tcctttgtgt 1560
gggtgactca cccgcccgct ctcccgagcg ccgcgtcctc cattttgagc tccctgcagc 1620
agggccggga agcggccatc tttccgctca cgcaactggt gccgaccggg ccagccttgc 1680
cgcccagggc ggggcgatac acggcggcgc gaggccaggc accagagcag gccggccagc 1740
ttgagactac ccccgtccga ttctcggtgg ccgcgctcgc aggccccgcc tcgccgaaca 1800
tgtgcgctgg gacgcacggg ccccgtcgcc gcccgcggcc ccaaaaaccg aaataccagt 1860
gtgcagatct tggcccgcat ttacaagact atcttgccag aaaaaaagcg tcgcagcagg 1920
tcatcaaaaa ttttaaatgg ctagagactt atcgaaagca gcgagacagg cgcgaaggtg 1980
ccaccagatt cgcacgcggc ggccccagcg cccaggccag gcctcaactc aagcacgagg 2040
cgaaggggct ccttaagcgc aaggcctcga actctcccac ccacttccaa cccgaagctc 2100
gggatcaaga atcacgtact gcagccaggg gcgtggaagt aattcaaggc acgcaagggc 2160
cataacccgt aaagaggcca ggcccgcggg aaccacacac ggcacttacc tgtgttctgg 2220
cggcaaaccc gttgcgaaaa agaacgttca cggcgactac tgcacttata tacggttctc 2280
ccccaccctc gggaaaaagg cggagccagt acacgacatc actttcccag tttaccccgc 2340
gccaccttct ctaggcaccg gttcaattgc cgacccctcc ccccaacttc tcggggactg 2400
tgggcgatgt gcgctctgcc cactgacggg caccggagcc gttacataac ttacggtaaa 2460
tggcccgcct ggctgaccgc ccaacgaccc ccgcccattg acgtcaataa tgacgtatgt 2520
tcccatagta acgccaatag ggactttcca ttgacgtcaa tgggtggagt atttacggta 2580
aactgcccac ttggcagtac atcaagtgta tcatatgcca agtacgcccc ctattgacgt 2640
caatgacggt aaatggcccg cctggcatta tgcccagtac atgaccttat gggactttcc 2700
tacttggcag tacatctacg tattagtcat cgctattacc atggtgatgc ggttttggca 2760
gtacatcaat gggcgtggat agcggtttga ctcacgggga tttccaagtc tccaccccat 2820
tgacgtcaat gggagtttgt tttggcacca aaatcaacgg gactttccaa aatgtcgtaa 2880
caactccgcc ccattgacgc aaatgggcgg taggcgtgta cggtgggagg tctatataag 2940
cagagctctc tggctaacta gagaacccac tgcttactgg cttatcgaaa tgccaccatg 3000
cgctcagcgg ccgcagctcc tcggagtccc gcggtggcca ccgagtctcg ccgcttcgcc 3060
gcagccaggt ggcccgggtg gcgctcgctc cagcggccgg cgcggcggag cgggcggggc 3120
ggcggtggcg cggccccggg accgtatccc tccgccgccc ctcccccgcc cggccccggc 3180
ccccctccct cccggcagag ctcgcctccc tccgcctcag actgttttgg tagcaacggc 3240
aacggcggcg gcgcgtttcg gcccggctcc cggcggctcc ttggtctcgg cgggcctccc 3300
cgccccttcg tcgtcctcct tctccccctc gccagcccgg gcgcccctcc ggccgcgcca 3360
acccgagcgt cacctttggg cgctcgcgcc tctccccctc gcagcggcgt ctccctcgct 3420
cgaccggctc ctggttgtcc acggcccgct tgcgaacctg tatatgggcc acttacgatg 3480
agtttgaagc cacaacaaca acagcagcaa caacaacagc aacagcaaca gcaacaacaa 3540
caacaacagc agcagcaaca acctccgcct gctgctgcaa atgtcagaaa accgggagga 3600
agcggactcc tcgcttcccc cgctgcagcc cccagtccca gctcttcctc cgtgtctagc 3660
agttccgcta ctgccccatc ctcagttgtg gcggcaacat ctgggggagg acgaccaggt 3720
ttgggcaggt gggtgtcggc acctccggcg cgcgggtggt ggccgatccg cattgctgtt 3780
cgaggccgca gtggagaagg cgcctgtgga acatcggtgg gtgagggctg gacccaggct 3840
ggaccctgga gatccggggt ggcggtgctg gtggcagggg gcgggcaccc tgcgcactta 3900
tcccaacccc cgccccaatt tcggaaatgc taggagagag agattgcagc aggggacgtg 3960
gtcgggttcc tgaaggcaga aaggcgggtg tttactagcg tctttttccc tcctaagccg 4020
gggttgtagt aggggctggg ggctcagtgt tgtcccggct aactgggttt gactcgaggg 4080
tgtgtttgtg caggagggcc tgttgggggt ggcgggcggt tgtcagttcg tatttcacga 4140
actaagaaaa tgcttagtgt tcaaagggag aaggaaacgt caatagactc cattccattg 4200
tggccggtgt ccttaacttc gggagtgccg ccagagctta ccaagggcac gcaagtccat 4260
ttcccttgtg cctcaagtcc atccgtgttg taggcactac tgtgccttct ttaggcctag 4320
gccgccggct tgacggcggg tgaccggcgt cctccttaaa taggcatctt gggctttgga 4380
aggtggaata agaggatttt tcattcaccc gagttttctt tttgaaaaca cattttcagc 4440
aacccatttc caaagaattt ttatttacag cagaaattcc ccatcaagag gaatcagctg 4500
gtttttaagg aattctgctg ccttcaaagg gggcggaaac agtcggttat ttgactttac 4560
acgccccgcc cccccttccc cttctctgag tctgaagcat cccaaacact acttagccaa 4620
actagttcag atgaagtgat cgtttcccca agtagggtaa cttcagtttc cctttttcgt 4680
tggcatctag cgaaaaatga aaaaatttaa aatacaactt ttatagaaaa ggatgtattc 4740
tgtttttact ttcttaggta ttaggaagag atttggcaga taattcaaca tgttcaaata 4800
tataaacatt aaaactaagg ttattaagtt gcattgacta ctaggcttaa aaattagatt 4860
ataagagaat ttgctcctga gtagtttgag tgatcaaaga tatttggaat gttttagtac 4920
cacaaggtct tttttctgtt ccttgaggct ttacaacaat ttaaggttaa tttagatttt 4980
tccttgcttt aagttctt 4998
<210> 16
<211> 23
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> target site
<400> 16
tgtgcaggag ggcctgttgg ggg 23
<210> 17
<211> 27
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> target site
<400> 17
tttcccttgt gcctcaagtc catccgt 27
<210> 18
<211> 81
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> target site
<400> 18
tttgtgcagg agggcctgtt gggggtgttt cccttgtgcc tcaagtccat ccgttttaag 60
gaattctgct gccttcaaag g 81
<210> 19
<211> 374
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> left homology arm
<400> 19
tccagcctcc cgcagcatcc ccgccccctc ccccggcggt caagatggag ggagcgggcg 60
gcctcccctc cccacgcgtg ttgggagggg ttctcgggta gcggcgatgg tcagccccgg 120
ctcccccttc cgcacgatcc tccgcccgca gcgtggggat gctcgggcag ctcctccact 180
cccggtttag gtgtgaacgt tggaggggtc tggaggctgt ggtggcgttt tccggaacat 240
gtccccctcc atgggggaca tctctggagg ggagaagtta gggccgcgtc ccccgtgccg 300
gttaaagggg taggcaccgg gctcctccgg aatcatcagg gtctgtcggg gctctctccc 360
cgccccctcc gagt 374
<210> 20
<211> 731
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> partial code sequence
<400> 20
ctgcccaggc cgggcctccc gccgccggag gtcgccgcga ccaccgagga gggagccgtg 60
gccgaggacg aggagaccga ggacgaggac ggcgaaggcg cggcggcggg cgacgctaga 120
aggccgctgc cgccgggctt gcggacattg gcagccgcgg gcggcggctg ctgctgctgc 180
tgctgctgct gctgttgctg ctgctgctgc tgctgctgct gctgctgctg ctgctggggc 240
ttcagcgaca tggtgagggg cccatacacc ggctcgcacg ccgggcgggg acagccggga 300
gccgggcgcg ccaaggagac gccggaacgc ggcggggacg cgcgggcgcc gagcggggag 360
gcgcgtgtag gagccgcggg aggtgcgccc ggggatgcga gcggaagcag cagcaccaca 420
aatggccggg gaggccctcc cagccccaac aagcgtctag acccagggcg aaaagctccc 480
ccaccatttc catttgaccc aaagcagtcg ctcgcggatg ggggtgagga ttgccttgag 540
ggtgggggcc ctggccccgg aggaggaggg gcggcgcttg gatatggtcc tggcgcagct 600
cccccaccac cccttccgga tctgcgcgct ggtcgctgca aactcctcca gccgggccac 660
ctggctgcgg cgaacctcct tgattccgtt gccaccgcag gggatctcgg cgctgccgca 720
gcgctccgca t 731
<210> 21
<211> 1182
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> promoter
<400> 21
tcacgacacc tgaaatggaa gaaaaaaact ttgaaccact gtctgaggct tgagaatgaa 60
ccaagatcca aactcaaaaa gggcaaattc caaggagaat tacatcaagt gccaagctgg 120
cctaacttca gtctccaccc actcagtgtg gggaaactcc atcgcataaa acccctcccc 180
ccaacctaaa gacgacgtac tccaaaagct cgagaactaa tcgaggtgcc tggacggcgc 240
ccggtactcc gtggagtcac atgaagcgac ggctgaggac ggaaaggccc ttttcctttg 300
tgtgggtgac tcacccgccc gctctcccga gcgccgcgtc ctccattttg agctccctgc 360
agcagggccg ggaagcggcc atctttccgc tcacgcaact ggtgccgacc gggccagcct 420
tgccgcccag ggcggggcga tacacggcgg cgcgaggcca ggcaccagag caggccggcc 480
agcttgagac tacccccgtc cgattctcgg tggccgcgct cgcaggcccc gcctcgccga 540
acatgtgcgc tgggacgcac gggccccgtc gccgcccgcg gccccaaaaa ccgaaatacc 600
agtgtgcaga tcttggcccg catttacaag actatcttgc cagaaaaaaa gcgtcgcagc 660
aggtcatcaa aaattttaaa tggctagaga cttatcgaaa gcagcgagac aggcgcgaag 720
gtgccaccag attcgcacgc ggcggcccca gcgcccaggc caggcctcaa ctcaagcacg 780
aggcgaaggg gctccttaag cgcaaggcct cgaactctcc cacccacttc caacccgaag 840
ctcgggatca agaatcacgt actgcagcca ggggcgtgga agtaattcaa ggcacgcaag 900
ggccataacc cgtaaagagg ccaggcccgc gggaaccaca cacggcactt acctgtgttc 960
tggcggcaaa cccgttgcga aaaagaacgt tcacggcgac tactgcactt atatacggtt 1020
ctcccccacc ctcgggaaaa aggcggagcc agtacacgac atcactttcc cagtttaccc 1080
cgcgccacct tctctaggca ccggttcaat tgccgacccc tccccccaac ttctcgggga 1140
ctgtgggcga tgtgcgctct gcccactgac gggcaccgga gc 1182
<210> 22
<211> 508
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> promoter
<400> 22
cgttacataa cttacggtaa atggcccgcc tggctgaccg cccaacgacc cccgcccatt 60
gacgtcaata atgacgtatg ttcccatagt aacgccaata gggactttcc attgacgtca 120
atgggtggag tatttacggt aaactgccca cttggcagta catcaagtgt atcatatgcc 180
aagtacgccc cctattgacg tcaatgacgg taaatggccc gcctggcatt atgcccagta 240
catgacctta tgggactttc ctacttggca gtacatctac gtattagtca tcgctattac 300
catggtgatg cggttttggc agtacatcaa tgggcgtgga tagcggtttg actcacgggg 360
atttccaagt ctccacccca ttgacgtcaa tgggagtttg ttttggcacc aaaatcaacg 420
ggactttcca aaatgtcgta acaactccgc cccattgacg caaatgggcg gtaggcgtgt 480
acggtgggag gtctatataa gcagagct 508
<210> 23
<211> 731
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> partial code sequence
<400> 23
atgcgctcag cggccgcagc tcctcggagt cccgcggtgg ccaccgagtc tcgccgcttc 60
gccgcagcca ggtggcccgg gtggcgctcg ctccagcggc cggcgcggcg gagcgggcgg 120
ggcggcggtg gcgcggcccc gggaccgtat ccctccgccg cccctccccc gcccggcccc 180
ggcccccctc cctcccggca gagctcgcct ccctccgcct cagactgttt tggtagcaac 240
ggcaacggcg gcggcgcgtt tcggcccggc tcccggcggc tccttggtct cggcgggcct 300
ccccgcccct tcgtcgtcct ccttctcccc ctcgccagcc cgggcgcccc tccggccgcg 360
ccaacccgag cgtcaccttt gggcgctcgc gcctctcccc ctcgcagcgg cgtctccctc 420
gctcgaccgg ctcctggttg tccacggccc gcttgcgaac ctgtatatgg gccacttacg 480
atgagtttga agccacaaca acaacagcag caacaacaac agcaacagca acagcaacaa 540
caacaacaac agcagcagca acaacctccg cctgctgctg caaatgtcag aaaaccggga 600
ggaagcggac tcctcgcttc ccccgctgca gcccccagtc ccagctcttc ctccgtgtct 660
agcagttccg ctactgcccc atcctcagtt gtggcggcaa catctggggg aggacgacca 720
ggtttgggca g 731
<210> 24
<211> 1255
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> Right homology arm
<400> 24
tccggcgcgc gggtggtggc cgatccgcat tgctgttcga ggccgcagtg gagaaggcgc 60
ctgtggaaca tcggtgggtg agggctggac ccaggctgga ccctggagat ccggggtggc 120
ggtgctggtg gcagggggcg ggcaccctgc gcacttatcc caacccccgc cccaatttcg 180
gaaatgctag gagagagaga ttgcagcagg ggacgtggtc gggttcctga aggcagaaag 240
gcgggtgttt actagcgtct ttttccctcc taagccgggg ttgtagtagg ggctgggggc 300
tcagtgttgt cccggctaac tgggtttgac tcgagggtgt gtttgtgcag gagggcctgt 360
tgggggtggc gggcggttgt cagttcgtat ttcacgaact aagaaaatgc ttagtgttca 420
aagggagaag gaaacgtcaa tagactccat tccattgtgg ccggtgtcct taacttcggg 480
agtgccgcca gagcttacca agggcacgca agtccatttc ccttgtgcct caagtccatc 540
cgtgttgtag gcactactgt gccttcttta ggcctaggcc gccggcttga cggcgggtga 600
ccggcgtcct ccttaaatag gcatcttggg ctttggaagg tggaataaga ggatttttca 660
ttcacccgag ttttcttttt gaaaacacat tttcagcaac ccatttccaa agaattttta 720
tttacagcag aaattcccca tcaagaggaa tcagctggtt tttaaggaat tctgctgcct 780
tcaaaggggg cggaaacagt cggttatttg actttacacg ccccgccccc ccttcccctt 840
ctctgagtct gaagcatccc aaacactact tagccaaact agttcagatg aagtgatcgt 900
ttccccaagt agggtaactt cagtttccct ttttcgttgg catctagcga aaaatgaaaa 960
aatttaaaat acaactttta tagaaaagga tgtattctgt ttttactttc ttaggtatta 1020
ggaagagatt tggcagataa ttcaacatgt tcaaatatat aaacattaaa actaaggtta 1080
ttaagttgca ttgactacta ggcttaaaaa ttagattata agagaatttg ctcctgagta 1140
gtttgagtga tcaaagatat ttggaatgtt ttagtaccac aaggtctttt ttctgttcct 1200
tgaggcttta caacaattta aggttaattt agatttttcc ttgctttaag ttctt 1255
<210> 25
<211> 3461
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> constructs
<400> 25
tttgtgcagg agggcctgtt gggggtgttt cccttgtgcc tcaagtccat ccgttttaag 60
gaattctgct gccttcaaag ggctggggtg ccgacaccca cctgcccagg ccgggcctcc 120
cgccgccgga ggtcgccgcg accaccgagg agggagccgt ggccgaggac gaggagaccg 180
aggacgagga cggcgaaggc gcggcggcgg gcgacgctag aaggccgctg ccgccgggct 240
tgcggacatt ggcagccgcg ggcggcggct gctgctgctg ctgctgctgc tgctgttgct 300
gctgctgctg ctgctgctgc tgctgctgct gctgctgggg cttcagcgac atggtgaggg 360
gcccatacac cggctcgcac gccgggcggg gacagccggg agccgggcgc gccaaggaga 420
cgccggaacg cggcggggac gcgcgggcgc cgagcgggga ggcgcgtgta ggagccgcgg 480
gaggtgcgcc cggggatgcg agcggaagca gcagcaccac aaatggccgg ggaggccctc 540
ccagccccaa caagcgtcta gacccagggc gaaaagctcc cccaccattt ccatttgacc 600
caaagcagtc gctcgcggat gggggtgagg attgccttga gggtgggggc cctggccccg 660
gaggaggagg ggcggcgctt ggatatggtc ctggcgcagc tcccccacca ccccttccgg 720
atctgcgcgc tggtcgctgc aaactcctcc agccgggcca cctggctgcg gcgaacctcc 780
ttgattccgt tgccaccgca ggggatctcg gcgctgccgc agcgctccgc atggtggcgg 840
tggcgaccgg tggatcccgg gcccgcggta ccgtcgactg cagaattcct cacgacacct 900
gaaatggaag aaaaaaactt tgaaccactg tctgaggctt gagaatgaac caagatccaa 960
actcaaaaag ggcaaattcc aaggagaatt acatcaagtg ccaagctggc ctaacttcag 1020
tctccaccca ctcagtgtgg ggaaactcca tcgcataaaa cccctccccc caacctaaag 1080
acgacgtact ccaaaagctc gagaactaat cgaggtgcct ggacggcgcc cggtactccg 1140
tggagtcaca tgaagcgacg gctgaggacg gaaaggccct tttcctttgt gtgggtgact 1200
cacccgcccg ctctcccgag cgccgcgtcc tccattttga gctccctgca gcagggccgg 1260
gaagcggcca tctttccgct cacgcaactg gtgccgaccg ggccagcctt gccgcccagg 1320
gcggggcgat acacggcggc gcgaggccag gcaccagagc aggccggcca gcttgagact 1380
acccccgtcc gattctcggt ggccgcgctc gcaggccccg cctcgccgaa catgtgcgct 1440
gggacgcacg ggccccgtcg ccgcccgcgg ccccaaaaac cgaaatacca gtgtgcagat 1500
cttggcccgc atttacaaga ctatcttgcc agaaaaaaag cgtcgcagca ggtcatcaaa 1560
aattttaaat ggctagagac ttatcgaaag cagcgagaca ggcgcgaagg tgccaccaga 1620
ttcgcacgcg gcggccccag cgcccaggcc aggcctcaac tcaagcacga ggcgaagggg 1680
ctccttaagc gcaaggcctc gaactctccc acccacttcc aacccgaagc tcgggatcaa 1740
gaatcacgta ctgcagccag gggcgtggaa gtaattcaag gcacgcaagg gccataaccc 1800
gtaaagaggc caggcccgcg ggaaccacac acggcactta cctgtgttct ggcggcaaac 1860
ccgttgcgaa aaagaacgtt cacggcgact actgcactta tatacggttc tcccccaccc 1920
tcgggaaaaa ggcggagcca gtacacgaca tcactttccc agtttacccc gcgccacctt 1980
ctctaggcac cggttcaatt gccgacccct ccccccaact tctcggggac tgtgggcgat 2040
gtgcgctctg cccactgacg ggcaccggag ccgttacata acttacggta aatggcccgc 2100
ctggctgacc gcccaacgac ccccgcccat tgacgtcaat aatgacgtat gttcccatag 2160
taacgccaat agggactttc cattgacgtc aatgggtgga gtatttacgg taaactgccc 2220
acttggcagt acatcaagtg tatcatatgc caagtacgcc ccctattgac gtcaatgacg 2280
gtaaatggcc cgcctggcat tatgcccagt acatgacctt atgggacttt cctacttggc 2340
agtacatcta cgtattagtc atcgctatta ccatggtgat gcggttttgg cagtacatca 2400
atgggcgtgg atagcggttt gactcacggg gatttccaag tctccacccc attgacgtca 2460
atgggagttt gttttggcac caaaatcaac gggactttcc aaaatgtcgt aacaactccg 2520
ccccattgac gcaaatgggc ggtaggcgtg tacggtggga ggtctatata agcagagctc 2580
tctggctaac tagagaaccc actgcttact ggcttatcga aatgccacca tgcgctcagc 2640
ggccgcagct cctcggagtc ccgcggtggc caccgagtct cgccgcttcg ccgcagccag 2700
gtggcccggg tggcgctcgc tccagcggcc ggcgcggcgg agcgggcggg gcggcggtgg 2760
cgcggccccg ggaccgtatc cctccgccgc ccctcccccg cccggccccg gcccccctcc 2820
ctcccggcag agctcgcctc cctccgcctc agactgtttt ggtagcaacg gcaacggcgg 2880
cggcgcgttt cggcccggct cccggcggct ccttggtctc ggcgggcctc cccgcccctt 2940
cgtcgtcctc cttctccccc tcgccagccc gggcgcccct ccggccgcgc caacccgagc 3000
gtcacctttg ggcgctcgcg cctctccccc tcgcagcggc gtctccctcg ctcgaccggc 3060
tcctggttgt ccacggcccg cttgcgaacc tgtatatggg ccacttacga tgagtttgaa 3120
gccacaacaa caacagcagc aacaacaaca gcaacagcaa cagcaacaac aacaacaaca 3180
gcagcagcaa caacctccgc ctgctgctgc aaatgtcaga aaaccgggag gaagcggact 3240
cctcgcttcc cccgctgcag cccccagtcc cagctcttcc tccgtgtcta gcagttccgc 3300
tactgcccca tcctcagttg tggcggcaac atctggggga ggacgaccag gtttgggcag 3360
gtgggtgtcg gcaccccagc tttgtgcagg agggcctgtt gggggtgttt cccttgtgcc 3420
tcaagtccat ccgttttaag gaattctgct gccttcaaag g 3461
<210> 26
<211> 22
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> primer
<400> 26
catcagaaag aataagggct gc 22
<210> 27
<211> 20
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> primer
<400> 27
tcacccttgc tctcagagac 20
<210> 28
<211> 20
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> primer
<400> 28
gcggtggcaa cggaatcaag 20
<210> 29
<211> 22
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> primer
<400> 29
cccgcttgcg aacctgtata tg 22
<210> 30
<211> 639
<212> PRT
<213> Pseudocladosporium hergelloides (Scytonema hoffmanii)
<400> 30
Met Ser Gln Ile Thr Ile Gln Ala Arg Leu Ile Ser Phe Glu Ser Asn
1 5 10 15
Arg Gln Gln Leu Trp Lys Leu Met Ala Asp Leu Asn Thr Pro Leu Ile
20 25 30
Asn Glu Leu Leu Cys Gln Leu Gly Gln His Pro Asp Phe Glu Lys Trp
35 40 45
Gln Gln Lys Gly Lys Leu Pro Ser Thr Val Val Ser Gln Leu Cys Gln
50 55 60
Pro Leu Lys Thr Asp Pro Arg Phe Ala Gly Gln Pro Ser Arg Leu Tyr
65 70 75 80
Met Ser Ala Ile His Ile Val Asp Tyr Ile Tyr Lys Ser Trp Leu Ala
85 90 95
Ile Gln Lys Arg Leu Gln Gln Gln Leu Asp Gly Lys Thr Arg Trp Leu
100 105 110
Glu Met Leu Asn Ser Asp Ala Glu Leu Val Glu Leu Ser Gly Asp Thr
115 120 125
Leu Glu Ala Ile Arg Val Lys Ala Ala Glu Ile Leu Ala Ile Ala Met
130 135 140
Pro Ala Ser Glu Ser Asp Ser Ala Ser Pro Lys Gly Lys Lys Gly Lys
145 150 155 160
Lys Glu Lys Lys Pro Ser Ser Ser Ser Pro Lys Arg Ser Leu Ser Lys
165 170 175
Thr Leu Phe Asp Ala Tyr Gln Glu Thr Glu Asp Ile Lys Ser Arg Ser
180 185 190
Ala Ile Ser Tyr Leu Leu Lys Asn Gly Cys Lys Leu Thr Asp Lys Glu
195 200 205
Glu Asp Ser Glu Lys Phe Ala Lys Arg Arg Arg Gln Val Glu Ile Gln
210 215 220
Ile Gln Arg Leu Thr Glu Lys Leu Ile Ser Arg Met Pro Lys Gly Arg
225 230 235 240
Asp Leu Thr Asn Ala Lys Trp Leu Glu Thr Leu Leu Thr Ala Thr Thr
245 250 255
Thr Val Ala Glu Asp Asn Ala Gln Ala Lys Arg Trp Gln Asp Ile Leu
260 265 270
Leu Thr Arg Ser Ser Ser Leu Pro Phe Pro Leu Val Phe Glu Thr Asn
275 280 285
Glu Asp Met Val Trp Ser Lys Asn Gln Lys Gly Arg Leu Cys Val His
290 295 300
Phe Asn Gly Leu Ser Asp Leu Ile Phe Glu Val Tyr Cys Gly Asn Arg
305 310 315 320
Gln Leu His Trp Phe Gln Arg Phe Leu Glu Asp Gln Gln Thr Lys Arg
325 330 335
Lys Ser Lys Asn Gln His Ser Ser Gly Leu Phe Thr Leu Arg Asn Gly
340 345 350
His Leu Val Trp Leu Glu Gly Glu Gly Lys Gly Glu Pro Trp Asn Leu
355 360 365
His His Leu Thr Leu Tyr Cys Cys Val Asp Asn Arg Leu Trp Thr Glu
370 375 380
Glu Gly Thr Glu Ile Val Arg Gln Glu Lys Ala Asp Glu Ile Thr Lys
385 390 395 400
Phe Ile Thr Asn Met Lys Lys Lys Ser Asp Leu Ser Asp Thr Gln Gln
405 410 415
Ala Leu Ile Gln Arg Lys Gln Ser Thr Leu Thr Arg Ile Asn Asn Ser
420 425 430
Phe Glu Arg Pro Ser Gln Pro Leu Tyr Gln Gly Gln Ser His Ile Leu
435 440 445
Val Gly Val Ser Leu Gly Leu Glu Lys Pro Ala Thr Val Ala Val Val
450 455 460
Asp Ala Ile Ala Asn Lys Val Leu Ala Tyr Arg Ser Ile Lys Gln Leu
465 470 475 480
Leu Gly Asp Asn Tyr Glu Leu Leu Asn Arg Gln Arg Arg Gln Gln Gln
485 490 495
Tyr Leu Ser His Glu Arg His Lys Ala Gln Lys Asn Phe Ser Pro Asn
500 505 510
Gln Phe Gly Ala Ser Glu Leu Gly Gln His Ile Asp Arg Leu Leu Ala
515 520 525
Lys Ala Ile Val Ala Leu Ala Arg Thr Tyr Lys Ala Gly Ser Ile Val
530 535 540
Leu Pro Lys Leu Gly Asp Met Arg Glu Val Val Gln Ser Glu Ile Gln
545 550 555 560
Ala Ile Ala Glu Gln Lys Phe Pro Gly Tyr Ile Glu Gly Gln Gln Lys
565 570 575
Tyr Ala Lys Gln Tyr Arg Val Asn Val His Arg Trp Ser Tyr Gly Arg
580 585 590
Leu Ile Gln Ser Ile Gln Ser Lys Ala Ala Gln Thr Gly Ile Val Ile
595 600 605
Glu Glu Gly Lys Gln Pro Ile Arg Gly Ser Pro His Asp Lys Ala Lys
610 615 620
Glu Leu Ala Leu Ser Ala Tyr Asn Leu Arg Leu Thr Arg Arg Ser
625 630 635
<210> 31
<211> 642
<212> PRT
<213> Anabaena cylindracea (Anabaena cylindrica)
<400> 31
Met Ser Val Ile Thr Ile Gln Cys Arg Leu Val Ala Glu Glu Asp Ser
1 5 10 15
Leu Arg Gln Leu Trp Glu Leu Met Ser Glu Lys Asn Thr Pro Phe Ile
20 25 30
Asn Glu Ile Leu Leu Gln Ile Gly Lys His Pro Glu Phe Glu Thr Trp
35 40 45
Leu Glu Lys Gly Arg Ile Pro Ala Glu Leu Leu Lys Thr Leu Gly Asn
50 55 60
Ser Leu Lys Thr Gln Glu Pro Phe Thr Gly Gln Pro Gly Arg Phe Tyr
65 70 75 80
Thr Ser Ala Ile Thr Leu Val Asp Tyr Leu Tyr Lys Ser Trp Phe Ala
85 90 95
Leu Gln Lys Arg Arg Lys Gln Gln Ile Glu Gly Lys Gln Arg Trp Leu
100 105 110
Lys Met Leu Lys Ser Asp Gln Glu Leu Glu Gln Glu Ser Gln Ser Ser
115 120 125
Leu Glu Val Ile Arg Asn Lys Ala Thr Glu Leu Phe Ser Lys Phe Thr
130 135 140
Pro Gln Ser Asp Ser Glu Ala Leu Arg Arg Asn Gln Asn Asp Lys Gln
145 150 155 160
Lys Lys Val Lys Lys Thr Lys Lys Ser Thr Lys Pro Lys Thr Ser Ser
165 170 175
Ile Phe Lys Ile Phe Leu Ser Thr Tyr Glu Glu Ala Glu Glu Pro Leu
180 185 190
Thr Arg Cys Ala Leu Ala Tyr Leu Leu Lys Asn Asn Cys Gln Ile Ser
195 200 205
Glu Leu Asp Glu Asn Pro Glu Glu Phe Thr Arg Asn Lys Arg Arg Lys
210 215 220
Glu Ile Glu Ile Glu Arg Leu Lys Asp Gln Leu Gln Ser Arg Ile Pro
225 230 235 240
Lys Gly Arg Asp Leu Thr Gly Glu Glu Trp Leu Glu Thr Leu Glu Ile
245 250 255
Ala Thr Phe Asn Val Pro Gln Asn Glu Asn Glu Ala Lys Ala Trp Gln
260 265 270
Ala Ala Leu Leu Arg Lys Thr Ala Asn Val Pro Phe Pro Val Ala Tyr
275 280 285
Glu Ser Asn Glu Asp Met Thr Trp Leu Lys Asn Asp Lys Asn Arg Leu
290 295 300
Phe Val Arg Phe Asn Gly Leu Gly Lys Leu Thr Phe Glu Ile Tyr Cys
305 310 315 320
Asp Lys Arg His Leu His Tyr Phe Gln Arg Phe Leu Glu Asp Gln Glu
325 330 335
Ile Leu Arg Asn Ser Lys Arg Gln His Ser Ser Ser Leu Phe Thr Leu
340 345 350
Arg Ser Gly Arg Ile Ala Trp Leu Pro Gly Glu Glu Lys Gly Glu His
355 360 365
Trp Lys Val Asn Gln Leu Asn Phe Tyr Cys Ser Leu Asp Thr Arg Met
370 375 380
Leu Thr Thr Glu Gly Thr Gln Gln Val Val Glu Glu Lys Val Thr Ala
385 390 395 400
Ile Thr Glu Ile Leu Asn Lys Thr Lys Gln Lys Asp Asp Leu Asn Asp
405 410 415
Lys Gln Gln Ala Phe Ile Thr Arg Gln Gln Ser Thr Leu Ala Arg Ile
420 425 430
Asn Asn Pro Phe Pro Arg Pro Ser Lys Pro Asn Tyr Gln Gly Lys Ser
435 440 445
Ser Ile Leu Ile Gly Val Ser Phe Gly Leu Glu Lys Pro Val Thr Val
450 455 460
Ala Val Val Asp Val Val Lys Asn Lys Val Ile Ala Tyr Arg Ser Val
465 470 475 480
Lys Gln Leu Leu Gly Glu Asn Tyr Asn Leu Leu Asn Arg Gln Arg Gln
485 490 495
Gln Gln Gln Arg Leu Ser His Glu Arg His Lys Ala Gln Lys Gln Asn
500 505 510
Ala Pro Asn Ser Phe Gly Glu Ser Glu Leu Gly Gln Tyr Val Asp Arg
515 520 525
Leu Leu Ala Asp Ala Ile Ile Ala Ile Ala Lys Lys Tyr Gln Ala Gly
530 535 540
Ser Ile Val Leu Pro Lys Leu Arg Asp Met Arg Glu Gln Ile Ser Ser
545 550 555 560
Glu Ile Gln Ser Arg Ala Glu Asn Gln Cys Pro Gly Tyr Lys Glu Gly
565 570 575
Gln Gln Lys Tyr Ala Lys Glu Tyr Arg Ile Asn Val His Arg Trp Ser
580 585 590
Tyr Gly Arg Leu Ile Glu Ser Ile Lys Ser Gln Ala Ala Gln Ala Gly
595 600 605
Ile Ala Ile Glu Thr Gly Lys Gln Ser Ile Arg Gly Ser Pro Gln Glu
610 615 620
Lys Ala Arg Asp Leu Ala Val Phe Thr Tyr Gln Glu Arg Gln Ala Ala
625 630 635 640
Leu Ile
<210> 32
<211> 208
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> left terminal of ShCas12k
<400> 32
tacagtgaca aattatctgt cgtcggtgac agattaatgt cattgtgact atttaattgt 60
cgtcgtgacc catcagcgtt gcttaattaa ttgatgacaa attaaatgtc atcaatataa 120
tatgctctgc aattattata caaagcaatt aaaacaagcg gataaaagga cttgctttca 180
acccacccct aagtttaata gttactga 208
<210> 33
<211> 219
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> right terminus of Cas12k
<400> 33
cgacagtcaa tttgtcatta tgaaaataca caaaagcttt ttcctatctt gcaaagcgac 60
agctaatttg tcacaatcac ggacaacgac atctattttg tcactgcaaa gaggttatgc 120
taaaactgcc aaagcgctat aatctatact gtataaggat tttactgatg acaataattt 180
gtcacaacga catataatta gtcactgtac acgtagaga 219
<210> 34
<211> 394
<212> PRT
<213> Vibrio cholerae (Vibrio cholerae)
<400> 34
Met Phe Leu Gln Arg Pro Lys Pro Tyr Ser Asp Glu Ser Leu Glu Ser
1 5 10 15
Phe Phe Ile Arg Val Ala Asn Lys Asn Gly Tyr Gly Asp Val His Arg
20 25 30
Phe Leu Glu Ala Thr Lys Arg Phe Leu Gln Asp Ile Asp His Asn Gly
35 40 45
Tyr Gln Thr Phe Pro Thr Asp Ile Thr Arg Ile Asn Pro Tyr Ser Ala
50 55 60
Lys Asn Ser Ser Ser Ala Arg Thr Ala Ser Phe Leu Lys Leu Ala Gln
65 70 75 80
Leu Thr Phe Asn Glu Pro Pro Glu Leu Leu Gly Leu Ala Ile Asn Arg
85 90 95
Thr Asn Met Lys Tyr Ser Pro Ser Thr Ser Ala Val Val Arg Gly Ala
100 105 110
Glu Val Phe Pro Arg Ser Leu Leu Arg Thr His Ser Ile Pro Cys Cys
115 120 125
Pro Leu Cys Leu Arg Glu Asn Gly Tyr Ala Ser Tyr Leu Trp His Phe
130 135 140
Gln Gly Tyr Glu Tyr Cys His Ser His Asn Val Pro Leu Ile Thr Thr
145 150 155 160
Cys Ser Cys Gly Lys Glu Phe Asp Tyr Arg Val Ser Gly Leu Lys Gly
165 170 175
Ile Cys Cys Lys Cys Lys Glu Pro Ile Thr Leu Thr Ser Arg Glu Asn
180 185 190
Gly His Glu Ala Ala Cys Thr Val Ser Asn Trp Leu Ala Gly His Glu
195 200 205
Ser Lys Pro Leu Pro Asn Leu Pro Lys Ser Tyr Arg Trp Gly Leu Val
210 215 220
His Trp Trp Met Gly Ile Lys Asp Ser Glu Phe Asp His Phe Ser Phe
225 230 235 240
Val Gln Phe Phe Ser Asn Trp Pro Arg Ser Phe His Ser Ile Ile Glu
245 250 255
Asp Glu Val Glu Phe Asn Leu Glu His Ala Val Val Ser Thr Ser Glu
260 265 270
Leu Arg Leu Lys Asp Leu Leu Gly Arg Leu Phe Phe Gly Ser Ile Arg
275 280 285
Leu Pro Glu Arg Asn Leu Gln His Asn Ile Ile Leu Gly Glu Leu Leu
290 295 300
Cys Tyr Leu Glu Asn Arg Leu Trp Gln Asp Lys Gly Leu Ile Ala Asn
305 310 315 320
Leu Lys Met Asn Ala Leu Glu Ala Thr Val Met Leu Asn Cys Ser Leu
325 330 335
Asp Gln Ile Ala Ser Met Val Glu Gln Arg Ile Leu Lys Pro Asn Arg
340 345 350
Lys Ser Lys Pro Asn Ser Pro Leu Asp Val Thr Asp Tyr Leu Phe His
355 360 365
Phe Gly Asp Ile Phe Cys Leu Trp Leu Ala Glu Phe Gln Ser Asp Glu
370 375 380
Phe Asn Arg Ser Phe Tyr Val Ser Arg Trp
385 390
<210> 35
<211> 640
<212> PRT
<213> Vibrio cholerae (Vibrio cholerae)
<400> 35
Met Gln Thr Leu Lys Glu Leu Ile Ala Ser Asn Pro Asp Asp Leu Thr
1 5 10 15
Thr Glu Leu Lys Arg Ala Phe Arg Pro Leu Thr Pro His Ile Ala Ile
20 25 30
Asp Gly Asn Glu Leu Asp Ala Leu Thr Ile Leu Val Asn Leu Thr Asp
35 40 45
Lys Thr Asp Asp Gln Lys Asp Leu Leu Asp Arg Ala Lys Cys Lys Gln
50 55 60
Lys Leu Arg Asp Glu Lys Trp Trp Ala Ser Cys Ile Asn Cys Val Asn
65 70 75 80
Tyr Arg Gln Ser His Asn Pro Lys Phe Pro Asp Ile Arg Ser Glu Gly
85 90 95
Val Ile Arg Thr Gln Ala Leu Gly Glu Leu Pro Ser Phe Leu Leu Ser
100 105 110
Ser Ser Lys Ile Pro Pro Tyr His Trp Ser Tyr Ser His Asp Ser Lys
115 120 125
Tyr Val Asn Lys Ser Ala Phe Leu Thr Asn Glu Phe Cys Trp Asp Gly
130 135 140
Glu Ile Ser Cys Leu Gly Glu Leu Leu Lys Asp Ala Asp His Pro Leu
145 150 155 160
Trp Asn Thr Leu Lys Lys Leu Gly Cys Ser Gln Lys Thr Cys Lys Ala
165 170 175
Met Ala Lys Gln Leu Ala Asp Ile Thr Leu Thr Thr Ile Asn Val Thr
180 185 190
Leu Ala Pro Asn Tyr Leu Thr Gln Ile Ser Leu Pro Asp Ser Asp Thr
195 200 205
Ser Tyr Ile Ser Leu Ser Pro Val Ala Ser Leu Ser Met Gln Ser His
210 215 220
Phe His Gln Arg Leu Gln Asp Glu Asn Arg His Ser Ala Ile Thr Arg
225 230 235 240
Phe Ser Arg Thr Thr Asn Met Gly Val Thr Ala Met Thr Cys Gly Gly
245 250 255
Ala Phe Arg Met Leu Lys Ser Gly Ala Lys Phe Ser Ser Pro Pro His
260 265 270
His Arg Leu Asn Ser Lys Arg Ser Trp Leu Thr Ser Glu His Val Gln
275 280 285
Ser Leu Lys Gln Tyr Gln Arg Leu Asn Lys Ser Leu Ile Pro Glu Asn
290 295 300
Ser Arg Ile Ala Leu Arg Arg Lys Tyr Lys Ile Glu Leu Gln Asn Met
305 310 315 320
Val Arg Ser Trp Phe Ala Met Gln Asp His Thr Leu Asp Ser Asn Ile
325 330 335
Leu Ile Gln His Leu Asn His Asp Leu Ser Tyr Leu Gly Ala Thr Lys
340 345 350
Arg Phe Ala Tyr Asp Pro Ala Met Thr Lys Leu Phe Thr Glu Leu Leu
355 360 365
Lys Arg Glu Leu Ser Asn Ser Ile Asn Asn Gly Glu Gln His Thr Asn
370 375 380
Gly Ser Phe Leu Val Leu Pro Asn Ile Arg Val Cys Gly Ala Thr Ala
385 390 395 400
Leu Ser Ser Pro Val Thr Val Gly Ile Pro Ser Leu Thr Ala Phe Phe
405 410 415
Gly Phe Val His Ala Phe Glu Arg Asn Ile Asn Arg Thr Thr Ser Ser
420 425 430
Phe Arg Val Glu Ser Phe Ala Ile Cys Val His Gln Leu His Val Glu
435 440 445
Lys Arg Gly Leu Thr Ala Glu Phe Val Glu Lys Gly Asp Gly Thr Ile
450 455 460
Ser Ala Pro Ala Thr Arg Asp Asp Trp Gln Cys Asp Val Val Phe Ser
465 470 475 480
Leu Ile Leu Asn Thr Asn Phe Ala Gln His Ile Asp Gln Asp Thr Leu
485 490 495
Val Thr Ser Leu Pro Lys Arg Leu Ala Arg Gly Ser Ala Lys Ile Ala
500 505 510
Ile Asp Asp Phe Lys His Ile Asn Ser Phe Ser Thr Leu Glu Thr Ala
515 520 525
Ile Glu Ser Leu Pro Ile Glu Ala Gly Arg Trp Leu Ser Leu Tyr Ala
530 535 540
Gln Ser Asn Asn Asn Leu Ser Asp Leu Leu Ala Ala Met Thr Glu Asp
545 550 555 560
His Gln Leu Met Ala Ser Cys Val Gly Tyr His Leu Leu Glu Glu Pro
565 570 575
Lys Asp Lys Pro Asn Ser Leu Arg Gly Tyr Lys His Ala Ile Ala Glu
580 585 590
Cys Ile Ile Gly Leu Ile Asn Ser Ile Thr Phe Ser Ser Glu Thr Asp
595 600 605
Pro Asn Thr Ile Phe Trp Ser Leu Lys Asn Tyr Gln Asn Tyr Leu Val
610 615 620
Val Gln Pro Arg Ser Ile Asn Asp Glu Thr Thr Asp Lys Ser Ser Leu
625 630 635 640
<210> 36
<211> 352
<212> PRT
<213> Vibrio cholerae (Vibrio cholerae)
<400> 36
Met Lys Leu Pro Thr Asn Leu Ala Tyr Glu Arg Ser Ile Asp Pro Ser
1 5 10 15
Asp Val Cys Phe Phe Val Val Trp Pro Asp Asp Arg Lys Thr Pro Leu
20 25 30
Thr Tyr Asn Ser Arg Thr Leu Leu Gly Gln Met Glu Ala Ala Ser Leu
35 40 45
Ala Tyr Asp Val Ser Gly Gln Pro Ile Lys Ser Ala Thr Ala Glu Ala
50 55 60
Leu Ala Gln Gly Asn Pro His Gln Val Asp Phe Cys His Val Pro Tyr
65 70 75 80
Gly Ala Ser His Ile Glu Cys Ser Phe Ser Val Ser Phe Ser Ser Glu
85 90 95
Leu Arg Gln Pro Tyr Lys Cys Asn Ser Ser Lys Val Lys Gln Thr Leu
100 105 110
Val Gln Leu Val Glu Leu Tyr Glu Thr Lys Ile Gly Trp Thr Glu Leu
115 120 125
Ala Thr Arg Tyr Leu Met Asn Ile Cys Asn Gly Lys Trp Leu Trp Lys
130 135 140
Asn Thr Arg Lys Ala Tyr Cys Trp Asn Ile Val Leu Thr Pro Trp Pro
145 150 155 160
Trp Asn Gly Glu Lys Val Gly Phe Glu Asp Ile Arg Thr Asn Tyr Thr
165 170 175
Ser Arg Gln Asp Phe Lys Asn Asn Lys Asn Trp Ser Ala Ile Val Glu
180 185 190
Met Ile Lys Thr Ala Phe Ser Ser Thr Asp Gly Leu Ala Ile Phe Glu
195 200 205
Val Arg Ala Thr Leu His Leu Pro Thr Asn Ala Met Val Arg Pro Ser
210 215 220
Gln Val Phe Thr Glu Lys Glu Ser Gly Ser Lys Ser Lys Ser Lys Thr
225 230 235 240
Gln Asn Ser Arg Val Phe Gln Ser Thr Thr Ile Asp Gly Glu Arg Ser
245 250 255
Pro Ile Leu Gly Ala Phe Lys Thr Gly Ala Ala Ile Ala Thr Ile Asp
260 265 270
Asp Trp Tyr Pro Glu Ala Thr Glu Pro Leu Arg Val Gly Arg Phe Gly
275 280 285
Val His Arg Glu Asp Val Thr Cys Tyr Arg His Pro Ser Thr Gly Lys
290 295 300
Asp Phe Phe Ser Ile Leu Gln Gln Ala Glu His Tyr Ile Glu Val Leu
305 310 315 320
Ser Ala Asn Lys Thr Pro Ala Gln Glu Thr Ile Asn Asp Met His Phe
325 330 335
Leu Met Ala Asn Leu Ile Lys Gly Gly Met Phe Gln His Lys Gly Asp
340 345 350
<210> 37
<211> 199
<212> PRT
<213> Vibrio cholerae (Vibrio cholerae)
<400> 37
Met Lys Trp Tyr Tyr Lys Thr Ile Thr Phe Leu Pro Glu Leu Cys Asn
1 5 10 15
Asn Glu Ser Leu Ala Ala Lys Cys Leu Arg Val Leu His Gly Phe Asn
20 25 30
Tyr Gln Tyr Glu Thr Arg Asn Ile Gly Val Ser Phe Pro Leu Trp Cys
35 40 45
Asp Ala Thr Val Gly Lys Lys Ile Ser Phe Val Ser Lys Asn Lys Ile
50 55 60
Glu Leu Asp Leu Leu Leu Lys Gln His Tyr Phe Val Gln Met Glu Gln
65 70 75 80
Leu Gln Tyr Phe His Ile Ser Asn Thr Val Leu Val Pro Glu Asp Cys
85 90 95
Thr Tyr Val Ser Phe Arg Arg Cys Gln Ser Ile Asp Lys Leu Thr Ala
100 105 110
Ala Gly Leu Ala Arg Lys Ile Arg Arg Leu Glu Lys Arg Ala Leu Ser
115 120 125
Arg Gly Glu Gln Phe Asp Pro Ser Ser Phe Ala Gln Lys Glu His Thr
130 135 140
Ala Ile Ala His Tyr His Ser Leu Gly Glu Ser Ser Lys Gln Thr Asn
145 150 155 160
Arg Asn Phe Arg Leu Asn Ile Arg Met Leu Ser Glu Gln Pro Arg Glu
165 170 175
Gly Asn Ser Ile Phe Ser Ser Tyr Gly Leu Ser Asn Ser Glu Asn Ser
180 185 190
Phe Gln Pro Val Pro Leu Ile
195
<210> 38
<211> 230
<212> PRT
<213> Vibrio cholerae (Vibrio cholerae)
<400> 38
Met Ala Thr Ser Leu Pro Thr Pro Ser Ala Ile Thr Thr Ser Ala Leu
1 5 10 15
Glu Tyr Ala Phe His Thr Pro Ala Arg Asn Leu Thr Lys Ser Arg Gly
20 25 30
Lys Asn Ile His Arg Tyr Val Ser Val Lys Met Ser Lys Arg Ile Thr
35 40 45
Val Glu Ser Thr Leu Glu Cys Asp Ala Cys Tyr His Phe Asp Phe Glu
50 55 60
Pro Ser Ile Val Arg Phe Cys Ala Gln Pro Ile Arg Phe Leu Tyr Tyr
65 70 75 80
Leu Asn Gly Gln Ser His Ser Tyr Val Pro Asp Phe Leu Val Gln Phe
85 90 95
Asp Thr Asn Glu Phe Val Leu Tyr Glu Val Lys Ser Ala Tyr Ala Lys
100 105 110
Asn Lys Pro Asp Phe Asp Val Glu Trp Glu Ala Lys Val Lys Ala Ala
115 120 125
Thr Glu Leu Gly Leu Glu Leu Glu Leu Val Glu Glu Ser Asp Ile Arg
130 135 140
Asp Thr Val Val Leu Asn Asn Leu Lys Arg Met His Arg Tyr Ala Ser
145 150 155 160
Lys Asp Glu Leu Asn Asn Val His Asn Ser Leu Leu Lys Ile Ile Lys
165 170 175
Tyr Asn Gly Ala Gln Ser Ala Arg Cys Leu Gly Glu Gln Leu Gly Leu
180 185 190
Lys Gly Arg Thr Val Leu Pro Ile Leu Cys Asp Leu Leu Ser Arg Cys
195 200 205
Leu Leu Asp Thr Arg Leu Asp Lys Pro Leu Ser Leu Glu Ser Arg Phe
210 215 220
Glu Leu Ala Ser Tyr Gly
225 230
<210> 39
<211> 603
<212> PRT
<213> Vibrio cholerae (Vibrio cholerae)
<400> 39
Met Ala Lys Lys Gly Phe Ser Ser Phe His Arg Lys Ala Val Ser Ser
1 5 10 15
Gln Asp Thr Leu Glu Ser Ile Glu Leu Val Ser Ser Ala Asn Cys Leu
20 25 30
Glu Ser Val Thr Tyr Gln Asp Ile Ser Ala Phe Pro Glu Thr Ile Ala
35 40 45
Val Glu Ile Asn Phe Arg Leu Ser Ile Leu Arg Phe Leu Ala Arg Lys
50 55 60
Cys Glu Thr Ile Val Ala Lys Ser Ile Glu Pro His Arg Val Glu Leu
65 70 75 80
Gln Gln Asn Tyr Ser Arg Lys Ile Pro Ser Ala Ile Thr Ile Tyr Arg
85 90 95
Trp Trp Leu Ala Phe Arg Lys Ser Asp Tyr Asn Pro Ile Ser Leu Ala
100 105 110
Pro Asn Ile Lys Asp Arg Gly Asn Arg Glu Thr Lys Val Ser Thr Val
115 120 125
Val Asp Ser Ile Met Glu Gln Ala Val Glu Arg Val Ile Ser Gly Arg
130 135 140
Lys Val Asn Val Ser Ser Ala Tyr Lys Arg Val Arg Arg Lys Val Arg
145 150 155 160
Gln Tyr Asn Leu Thr His Gly Thr Lys Tyr Thr Tyr Pro Lys Tyr Glu
165 170 175
Ser Val Arg Lys Arg Val Lys Lys Lys Thr Pro Phe Glu Leu Leu Ala
180 185 190
Ala Gly Lys Gly Glu Arg Val Ala Lys Arg Glu Phe Arg Arg Met Gly
195 200 205
Lys Lys Ile Leu Thr Ser Ser Val Leu Glu Arg Val Glu Ile Asp His
210 215 220
Thr Val Val Asp Leu Phe Ala Val His Glu Glu Tyr Arg Ile Pro Leu
225 230 235 240
Gly Arg Pro Trp Leu Thr Gln Leu Val Asp Cys Tyr Ser Lys Ala Val
245 250 255
Ile Gly Phe Tyr Leu Gly Phe Glu Pro Pro Ser Tyr Val Ser Val Ser
260 265 270
Leu Ala Leu Lys Asn Ala Ile Gln Arg Lys Asp Asp Leu Ile Ser Ser
275 280 285
Tyr Glu Ser Ile Glu Asn Glu Trp Leu Cys Tyr Gly Ile Pro Asp Leu
290 295 300
Leu Val Thr Asp Asn Gly Lys Glu Phe Leu Ser Lys Ala Phe Asp Gln
305 310 315 320
Ala Cys Glu Ser Leu Leu Ile Asn Val His Gln Asn Lys Val Glu Thr
325 330 335
Pro Asp Asn Lys Pro His Val Glu Arg Asn Tyr Gly Thr Ile Asn Thr
340 345 350
Ser Leu Leu Asp Asp Leu Pro Gly Lys Ser Phe Ser Gln Tyr Leu Gln
355 360 365
Arg Glu Gly Tyr Asp Ser Val Gly Glu Ala Thr Leu Thr Leu Asn Glu
370 375 380
Ile Arg Glu Ile Tyr Leu Ile Trp Leu Val Asp Ile Tyr His Lys Lys
385 390 395 400
Pro Asn Gln Arg Gly Thr Asn Cys Pro Asn Val Ala Trp Lys Lys Gly
405 410 415
Cys Gln Glu Trp Glu Pro Glu Glu Phe Ser Gly Ser Lys Asp Glu Leu
420 425 430
Asp Phe Lys Phe Ala Ile Val Asp Tyr Lys Gln Leu Thr Lys Val Gly
435 440 445
Ile Thr Val Tyr Lys Glu Leu Ser Tyr Ser Asn Asp Arg Leu Ala Glu
450 455 460
Tyr Arg Gly Lys Lys Gly Asn His Lys Val Gln Phe Lys Tyr Asn Pro
465 470 475 480
Glu Cys Met Ala Val Ile Trp Val Leu Asp Glu Asp Met Asn Glu Tyr
485 490 495
Phe Thr Val Asn Ala Ile Asp Tyr Glu Tyr Ala Ser Arg Val Ser Leu
500 505 510
Trp Gln His Lys Tyr Asn Met Lys Tyr Gln Ala Glu Leu Asn Ser Ala
515 520 525
Glu Tyr Asp Glu Asp Lys Glu Ile Asp Ala Glu Ile Lys Ile Glu Glu
530 535 540
Ile Ala Asp Arg Ser Ile Val Lys Thr Asn Lys Ile Arg Ala Arg Arg
545 550 555 560
Arg Gly Ala Arg His Gln Glu Asn Ser Ala Arg Ala Lys Ser Ile Ser
565 570 575
Asn Ala Asn Pro Ala Ser Ile Gln Lys His Glu Asp Glu Ile Val Ser
580 585 590
Ala Asp Asn Asp Asp Trp Asp Ile Asp Tyr Val
595 600
<210> 40
<211> 330
<212> PRT
<213> Vibrio cholerae (Vibrio cholerae)
<400> 40
Met Ser Glu Thr Arg Glu Ala Arg Ile Ser Arg Ala Lys Arg Ala Phe
1 5 10 15
Val Ser Thr Pro Ser Val Arg Lys Ile Leu Ser Tyr Met Asp Arg Cys
20 25 30
Arg Asp Leu Ser Asp Leu Glu Ser Glu Pro Thr Cys Met Met Val Tyr
35 40 45
Gly Ala Ser Gly Val Gly Lys Thr Thr Val Ile Lys Lys Tyr Leu Asn
50 55 60
Gln Asn Arg Arg Glu Ser Glu Ala Gly Gly Asp Ile Ile Pro Val Leu
65 70 75 80
His Ile Glu Leu Pro Asp Asn Ala Lys Pro Val Asp Ala Ala Arg Glu
85 90 95
Leu Leu Val Glu Met Gly Asp Pro Leu Ala Leu Tyr Glu Thr Asp Leu
100 105 110
Ala Arg Leu Thr Lys Arg Leu Thr Glu Leu Ile Pro Ala Val Gly Val
115 120 125
Lys Leu Ile Ile Ile Asp Glu Phe Gln His Leu Val Glu Glu Arg Ser
130 135 140
Asn Arg Val Leu Thr Gln Val Gly Asn Trp Leu Lys Met Ile Leu Asn
145 150 155 160
Lys Thr Lys Cys Pro Ile Val Ile Phe Gly Met Pro Tyr Ser Lys Val
165 170 175
Val Leu Gln Ala Asn Ser Gln Leu His Gly Arg Phe Ser Ile Gln Val
180 185 190
Glu Leu Arg Pro Phe Ser Tyr Gln Gly Gly Arg Gly Val Phe Lys Thr
195 200 205
Phe Leu Glu Tyr Leu Asp Lys Ala Leu Pro Phe Glu Lys Gln Ala Gly
210 215 220
Leu Ala Asn Glu Ser Leu Gln Lys Lys Leu Tyr Ala Phe Ser Gln Gly
225 230 235 240
Asn Met Arg Ser Leu Arg Asn Leu Ile Tyr Gln Ala Ser Ile Glu Ala
245 250 255
Ile Asp Asn Gln His Glu Thr Ile Thr Glu Glu Asp Phe Val Phe Ala
260 265 270
Ser Lys Leu Thr Ser Gly Asp Lys Pro Asn Ser Trp Lys Asn Pro Phe
275 280 285
Glu Glu Gly Val Glu Val Thr Glu Asp Met Leu Arg Pro Pro Pro Lys
290 295 300
Asp Ile Gly Trp Glu Asp Tyr Leu Arg His Ser Thr Pro Arg Val Ser
305 310 315 320
Lys Pro Gly Arg Asn Lys Asn Phe Phe Glu
325 330
<210> 41
<211> 105
<212> DNA
<213> Vibrio cholerae (Vibrio cholerae)
<400> 41
tgttgatgca accataaagt gatatttaat aattatttat aatcagcaac ttaaccacaa 60
aacaaccata tattgatatc tcacaaaaca accataagtt gatat 105
<210> 42
<211> 60
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> guide RNA
<220>
<221> misc_feature
<222> (9)..(40)
<223> n is a, c, g or t
<400> 42
ctgataacnn nnnnnnnnnn nnnnnnnnnn nnnnnnnnnn gtgaactgcc gagtaggtag 60
<210> 43
<211> 47
<212> DNA
<213> Vibrio cholerae (Vibrio cholerae)
<400> 43
aattatcaat ttatgggtgt aattatcatt ttatggttgt atcaaca 47
<210> 44
<211> 258
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> guide RNA
<220>
<221> misc_feature
<222> (236)..(258)
<223> n is a, c, g or t
<400> 44
tattaatagc gccgcaattc atgctgcttg cagcctctga attttgttaa atgagggtta 60
gtttgactgt ataaatacag tcttgctttc tgaccctggt agctgctcac cctgatgctg 120
ctgtcaatag acaggatagg tgcgctccca gcaataaggg cgcggatgta ctgctgtagt 180
ggctactgaa tcacccccga tcaaggggga accctccaaa aggtgggttg aaagtnnnnn 240
nnnnnnnnnn nnnnnnnn 258
<210> 45
<211> 22
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> primer
<400> 45
tgggccactt acgatgagtt tg 22
<210> 46
<211> 20
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> primer
<400> 46
ctgtggaaca tcggtgggtg 20
<210> 47
<211> 24
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> primer
<400> 47
ttggctaagt agtgtttggg atgc 24
<210> 48
<211> 22
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> primer
<400> 48
agtagtgttt gggatgcttc ag 22
<210> 49
<211> 47
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> SOD1 shRNA
<400> 49
ggcctgcatg gattccatgt tcaagagaca tggaatccat gcaggcc 47
<210> 50
<211> 1596
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> constructs
<400> 50
gaattcgcgg ccgcttctag aggtttgggg ccagagtggg cgaggcgcgg aggtctggcc 60
tataaagtag tcgcggagac ggggtgctgg tttgcgtcgt agtctcctgc agcgtctggg 120
gtttccgttg cagtcctcgg aaccaggacc tcggcgtggc ctagcgagtt gccaccatgg 180
cgacgaaggc cgtgtgcgtg ctgaagggcg acggcccagt gcagggcatc atcaatttcg 240
agcagaagga aagtaatgga ccagtgaagg tgtggggaag cattaaagga ctgactgaag 300
gtttacacgg ctttcatgtt catgagtttg gagataatac agcaggctgt accagtgcag 360
gtcctcactt taatcctcta tccagaaaac acggtgggcc aaaggatgaa gagaggcatg 420
ttggagactt gggcaatgtg actgctgaca aagatggtgt ggccgatgtg tctattgaag 480
attctgtgat ctcactctca ggagaccatt gcatcattgg ccgcacactg gtggtccatg 540
aaaaagcaga tgacttgggc aaaggtggaa atgaagaaag tacaaagaca ggaaacgctg 600
gaagtcgttt ggcttgtggt gtaattggga tcgcccaata aacattccct tggatgtagt 660
ctgaggcccc ttaactcatc tgttatcctg ctagctgtag aaatgtatcc tgataaacat 720
taaacactgt aatcttaaaa gtgtaattgt gtgacttttt cagagttgct ttaaagtacc 780
tgtagtgaga aactgattta tgatcacttg gaagatttgt atagttttat aaaactcagt 840
taaaatgtct gtttcaatga cctgtatttt gccagactta aatcacagat gggtattaaa 900
cttgtcagaa tttctttgtc attcaagcct gtgaataaaa accctgtatg gcacttatta 960
tgaggctatt aaaagaatcc aaattcaaac taaaaacttg tttattgcag cttataatgg 1020
ttacaaataa agcaatagca tcacaaattt cacaaataaa gcattttttt cactgcattc 1080
tagttgtggt ttgtccaaac tcatcaatgt atcttatcat gtctggatca agcttgaggg 1140
cctatttccc atgattcctt catatttgca tatacgatac aaggctgtta gagagataat 1200
tggaattaat ttgactgtaa acacaaagat attagtacaa aatacgtgac gtagaaagta 1260
ataatttctt gggtagtttg cagttttaaa attatgtttt aaaatggact atcatatgct 1320
taccgtaact tgaaagtatt tcgatttctt ggctttatat atcttgtgga aaggacgaaa 1380
caccggcctg catggattcc atgttcaaga gacatggaat ccatgcaggc cttttttgaa 1440
ttctcgacct cgagacaaat ggcagtattc atccacaatt ttaaaagaaa aggggggatt 1500
ggggggtaca gtgcagggga aagaatagta gacataatag caacagacat acaaactaaa 1560
gaattacaaa aacaaattac aaaaattcaa aatttt 1596
<210> 51
<211> 2139
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> constructs
<400> 51
gccaccatgg atgtattcat gaaaggactt tcaaaggcca aggagggagt tgtggctgct 60
gctgagaaaa ccaaacaggg tgtggcagaa gcagcaggaa agacaaaaga gggtgttctc 120
tatgtaggct ccaaaaccaa ggagggagtg gtgcatggtg tggcaacagt ggctgagaag 180
accaaagagc aagtgacaaa tgttggagga gcagtggtga cgggtgtgac agcagtagcc 240
cagaagacag tggagggagc agggagcatt gcagcagcca ctggctttgt caaaaaggac 300
cagttgggca agaatgaaga aggagcccca caggaaggaa ttctggaaga tatgcctgtg 360
gatcctgaca atgaggctta tgaaatgcct tctgaggaag gctaccagga ttatgaacct 420
gaagcctaaa acttgtttat tgcagcttat aatggttaca aataaagcaa tagcatcaca 480
aatttcacaa ataaagcatt tttttcactg cattctagtt gtggtttgtc caaactcatc 540
aatgtatctt atcatgtctg gatcggggtt ggggttgcgc cttttccaag gcagccctgg 600
gtttgcgcag ggacgcggct gctctgggcg tggttccggg aaacgcagcg gcgccgaccc 660
tgggtctcgc acattcttca cgtccgttcg cagcgtcacc cggatcttcg ccgctaccct 720
tgtgggcccc ccggcgacgc ttcctgctcc gcccctaagt cgggaaggtt ccttgcggtt 780
cgcggcgtgc cggacgtgac aaacggaagc cgcacgtctc actagtaccc tcgcagacgg 840
acagcgccag ggagcaatgg cagcgcgccg accgcgatgg gctgtggcca atagcggctg 900
ctcagcaggg cgcgccgaga gcagcggccg ggaaggggcg gtgcgggagg cggggtgtgg 960
ggcggtagtg tgggccctgt tcctgcccgc gcggtgttcc gcattctgca agcctccgga 1020
gcgcacgtcg gcagtcggct ccctcgttga ccgaatcacc gacctctctc cccagctctg 1080
gctaactaga gaacccactg cttactggct tatcgaaatg ccaccatgga tgtattcatg 1140
aaaggacttt caaaggccaa ggagggagtt gtggctgctg ctgagaaaac caaacagggt 1200
gtggcagaag cagcaggaaa gacaaaagag ggtgttctct atgtaggctc caaaaccaag 1260
gagggagtgg tgcatggtgt ggcaacagtg gctgagaaga ccaaagagca agtgacaaat 1320
gttggaggag cagtggtgac gggtgtgaca gcagtagccc agaagacagt ggagggagca 1380
gggagcattg cagcagccac tggctttgtc aaaaaggacc agttgggcaa ggaaggctac 1440
caggattatg aacctgaagc ctaactgtgc cttctagttg ccagccatct gttgtttgcc 1500
cctcccccgt gccttccttg accctggaag gtgccactcc cactgtcctt tcctaataaa 1560
atgaggaaat tgcatcgcat tgtctgagta ggtgtcattc tattctgggg ggtggggtgg 1620
ggcaggacag caagggggag gattgggaag agaatagcag gcatgctggg gaaagcttga 1680
gggcctattt cccatgattc cttcatattt gcatatacga tacaaggctg ttagagagat 1740
aattggaatt aatttgactg taaacacaaa gatattagta caaaatacgt gacgtagaaa 1800
gtaataattt cttgggtagt ttgcagtttt aaaattatgt tttaaaatgg actatcatat 1860
gcttaccgta acttgaaagt atttcgattt cttggcttta tatatcttgt ggaaaggacg 1920
aaacaccggg tatcaagact acgaacttca agagagttcg tagtcttgat accctttttt 1980
gaattctcga cctcgagaca aatggcagta ttcatccaca attttaaaag aaaagggggg 2040
attggggggt acagtgcagg ggaaagaata gtagacataa tagcaacaga catacaaact 2100
aaagaattac aaaaacaaat tacaaaaatt caaaatttt 2139
<210> 52
<211> 7362
<212> DNA
<213> Intelligent (Homo sapiens)
<400> 52
gtaggtaaac cccaaatgtc agtttggtgc ttgttcatga gtgatgggtt aggataatca 60
atactctaaa tgctggtagt tctctctctt gattcatttt tgcatcattg cttgtcaaaa 120
aggtggactg agtcagaggt atgtgtaggt aggtgaatgt gaacgtgtgt atttgagcta 180
atagtaaaaa atgcgactgt ttgcttttcc agatttttaa ttttgcccta atatttatga 240
ctttttaaaa atgaatgttt ctgtacctac ataattctat ttcagagaac agttttaaaa 300
actcatagtc ttttaaaaaa taatcaagaa tattcttaag aatcaaaatc attgatggat 360
ctgtgatttc ttttaccatc atgaaaaatg tttgtcaatt ttaatccatt ctgattttta 420
aaatatgact ttgatatgcc cctgtgatgt gtataaagag acctatttgt ggccctaaaa 480
tggaaagaac agattagtct ttgatagagt tacttcatgt gatcatttgg tctctgtgaa 540
cactgaggac agagaaaagt gcttgagggc tgctactaat ctctcagaaa catttgtata 600
gttcatccat caaatgacac acatactaaa agaataaaga aattgatgct tattacctac 660
ttgttcctaa agttccacct tggggtatac acccaaactc tgactctctt ttctgtaact 720
tgaactgtat tcaattgagt gttattttac aaaccacttt gaattccttg gaaaagaata 780
gacacacact ctcatccaca ggcatagaca cacacactca acacagacac attgcccatt 840
cttcctctct tctttctcct ctgagctttt tcacattctc tggtggcaac tatagcagta 900
agagtcacag gatgaacagt caggtggagg atgaccacat tgagttgcct agctgaaaca 960
tgtgctccgt ctatgtctgc aaagtgaaag aaagctacac tatctcttca acatagatca 1020
gtgggggaaa ttttatactt gggatgattt atatgaatgc atctcatcaa agttcacaac 1080
acattttttt ttcagttttt tattttcagt ttttagagtc agggccttgc tctgtcgccc 1140
aggctggact gcagtgatgc tatcatagct cactgcatcc ttgaattcct gggctcaagt 1200
catgccccca cctcagcctc ctgagtagcc aggattatag gcatgtgcca ctgcctcatt 1260
atttagactt ttcttatgtt gacttaatct tcccacaaat cttcaattaa attacttttt 1320
ttctacctta aaacatattt tcagaaagtc attgaaatag ggtgttacaa gaggaaaaaa 1380
ttgatgagtt aattttaaat attttatgaa gtgtgaatta taccttttta gatggaattt 1440
ggaatactga atcagtgaca tgcagtttat caatatcttt ccgtttgtcc tcagatttcc 1500
aagttctgca agcacaagtt tctttgactt agttaccttt taactgttca ttgaaatcat 1560
tttcaatgtc tctcatggca tttaacacat agcacattct ataaattttt tattggttac 1620
attctgagtt ctaattgaga gttgaactta cacacagaat ttaagataaa aaatgaccat 1680
gtgaagacac aatagtatag tccagggatt ggcaaaattt tgggtaagga atcagatagc 1740
acgtatttta agccatgaga tctatgtctt ggccaggtgc cgtggctcag gtctttaatc 1800
ccagcacttt gagagcccga ggctggtgga tcacttgagc ccaggggttt gagaccagcc 1860
tgggccacat ggtgaaaccc tgtgtctaca aacaacgcaa aaattagccg ggtatggtag 1920
catgcatgtg tattgccagc tacccaggag gctgaggtag gaggatggct tgagccatac 1980
agctcactgc agaggttgca gtgagctgag atcgagccac tgcactccag cctgggtggc 2040
agagtgatac cctgtctaaa aaaaagaaaa aaaaatctat gtctcaattc tgctgttgaa 2100
gtgtgaaggt agtcataaac aataactagt gtggctgtgt cccaataaaa cttcatttat 2160
caaaacaggt ggtgggctgg aattgtcttg tatgttgtag cttgctgact actgatagag 2220
tggaaagaac atgcactaat cacacaaacc aaagttttag ttgagactac atcacttatc 2280
acctttaggg tcttggggaa gcgtacttaa catctctgag catcacttcc ctgattagta 2340
aaaaatatga tttagaaaac tgcaactacc ttgcagtttt tgtgggaatg tcataataag 2400
acaggacata tgaataattg agcacacttt tatatatagg aaccatggtt attattatca 2460
aataaactct ccaacggaat aattactttg ccaacacgtt ttccatttat tcttttatcc 2520
ttcattacat aactagtttg aaagattgga ggcgaccaaa gaccatttta taatttcact 2580
tatggctgaa gatgtttggt agaagcctca taagaaaagt aatctcattc ctttataaga 2640
atatactttt aacaactact ttttaactca ttgaagaact accttaatga tcagtgttat 2700
ttttatgggt tttgttccct ccatttttgt tatctgcgta caccaatttt caatcaacat 2760
acttcaattt aatagacaaa aatttcttca aatgactcag aaattaatta gatctaaatc 2820
caaaagcaga aagatttaat tatctttata taatgctcag taatataaat gcaataaata 2880
caagaaaatg atgatctttg agtgtcttcc aatgccactc tgctcaataa gcagcagtgg 2940
ccatcagtga aattgatagc aaattctcaa gtcaaaatgt gcttcacctc actaagctga 3000
caaagtcaac ataacatgca caacagggat aactgagttc tcaaaactct caggtattac 3060
ttctgacctt cttctccact ctgtgctctt ttgaggttgg gaagacaaga tagggtgtgt 3120
gtgggacacc tccgctcagg gaagccatca gctctggtgt ccctacagca tttatacctt 3180
gctagtcaca taaccacttg gcacctattt tgtaggtgta cgttatcaat tacagattac 3240
tcataaatta aaggctaacc atcaattaca gattattagt aaataattat gacctcaaag 3300
aacaactgat tggtttgata catggtaacc ttatgaggac tctcatttat ctcgtttttt 3360
taagttatat acctatctct ttggggttgc actacaaaaa tataaaatat gttgcataag 3420
atatttataa aaaataatta attataagtt ctaatggtgt ggtttagtgg cattcttttt 3480
tttttctttt tttctgagat agggtctcaa tctgtcattt cactccaggc tgaagtgcag 3540
tggtgtgatc tcggctcact gcaacctccg cctcctgggt tcaagttatt ctcctgactc 3600
agcctcctga gtagctgaaa ttacaggcat gcaccaccat gcccggctaa tttttgtatt 3660
tttagtagag atggggtttc accatgttag ccaggatggt ctcgaactcc tgatctcatc 3720
atccccgacc tcggcctccc aaaatgctgg gattacaggc gtgagccatt gcacccggcc 3780
tagtggcatt cttttttaaa aataaattta attgtgtata tttagggtat gcaacatgat 3840
gctatcagat acattagaca ctaaaaaatt actatattga agcaaattaa tatattcata 3900
atctctcata gttacctttt ttgttgtttt tgtggcaagg gcagctaaaa tccacttatt 3960
tatcatgaat ctcaaatata gtacaatttt atcacctaca gtcctcatac attagatctg 4020
tacacttttt catcttacac atctgctact tgcttggatc ctatggccta tatgtcccta 4080
ttttctacct acttttccac ccctattaac cctgtttttt acgtagtctc tgtatatttg 4140
aattttgttt caagcttcca catatatgtg agataatgta atatttttct ttctgtgttt 4200
ggcttatttc acttagcata attttgtctg ggttcatcca tgttgtaaat ggtaggatct 4260
tgttttttta gggctgactg atattccatt gtatctatgt accacaatct ttttatctac 4320
ctatctatca gtagacactt tagttgtggc tattatgttt ttcttttttt cttttttgga 4380
gacagggtct tgctgtcacc caggctgcaa tggagtggtg ttatcatagc tcactgtaac 4440
ctcaaacttc tgggctcaag agatcctcct gccttggcct cccaagtagc tgagactaca 4500
ggcatacatt accatgcctg gctaattttt aatatttttt gtagatatag catctcactc 4560
tgttgcccag actggtctca aactcctaat tcaaatttag aatagagtat gacaattctg 4620
taaaatataa aaaacatgtc cactccgtat aggaagttat acaatgagaa gaagacaaac 4680
actatttaca ttactcttga taagtttttt acaaagaaat aaaacacttt aatttctaat 4740
gttttaaatt ctggtttgct aaataaataa atattagttt tagtgttttt aaaattcctt 4800
atatagttat aagtgatctt cctgcctcag cctcccaaag cactgggatt ccaagcaaga 4860
gccactgtgt tggggccctt ggaaacagat atgctgaaat cttttcttgt ggatctacac 4920
ccagaagagg gattgctggg tcatatgcta ctctattttt aatttttctt ttatttttag 4980
tgaatatgta ataattgtat ataattgtgg gatccagaat tatatttcca tacatgtata 5040
caatgtgtga taatcaaatt agggtaatta acatatccat tacctgaaac atttatcatt 5100
cctttgtggt gggaacagta aaaattaaaa attctctctt ctagattttt gaacatatgc 5160
aataaactat tgttaagtat atcaccctac agtactacag aatgctagaa ctcattcctc 5220
atatttggct ccaatttcat attctttaac caacctctcc atatcctccc ctccctctta 5280
ccgttgtcag cctctaataa tcataattct actctctact tctatctcat tgtctttgat 5340
ttagaatatg tttcataatt taaccaaagg tcaaattctt aggtactgct aaggcaaaga 5400
acaaagatcg cattccagct gttagacatt tcttactact agtcattttt aagacaacat 5460
ggggtgcagg tggtgaggat gagagataga gattgaaaca tattctctta aatatcagct 5520
gttctcactc tgcatagttc cagcacaaac aaattccagg tactatggtt agttaaataa 5580
caccagccac taacaacaca attcaaattt ctgttaccac agtataccga aagtcattgc 5640
ataaagtaca aactttgctg ctaactcttc agccttcaaa tcattacata aataacagaa 5700
acccattata atcagtgaca aaaccacagc acttctttca aagctttttg gagattggtt 5760
gcttcacatc tgttatgcag ttcatacaga cagcaatgcc cggacttgtg tggccacatt 5820
gtctcccagt ggtgagccca tgtgatgttt cacgaaaatg cgcaatcaaa agaggaaact 5880
ggccagcaaa gatgaaagag tagcaaacaa aggaagtgaa acattctgga agtaaaattt 5940
gaatcaaaca taagttgatg tatacaggaa gtagctaccc tgaggatgtt gtcactgctg 6000
caattcagga gactctaaat atgcagtcag aggaacgtag tgaggtgaag gtatccgtat 6060
aatggggaaa gaggttgtga taaagagtga aggtgtccca gaggaagtgt tgctgaaaaa 6120
tacaccttat gttaaataca ctgtcagtat atcatgacat taaagtgcaa atgataacat 6180
tttgtaaact gatccaaact taaaaaggag tatgataatt ctgtaaaaca taaaaatcat 6240
gccgattcca taaattatac agtgtgaatt acactgaaaa atccaacatt agagaggata 6300
tgaatacaat tttttacaag cataatttta ataatacaca taataattat ttgtattcaa 6360
gtttagtaat gttcaaggtt tggaagaaat tctgatcctg tgtagagacc ctagtttgaa 6420
tgtgcttata gcctattatt acatgtgtaa tgttacataa attacttaac tcggattttt 6480
aatttcatca gctatttaaa atgggcataa tataactata ttaaatggct gttatgaaga 6540
ttaaataaga tgatatgtaa aatgtgtttt ttgtttgttt gtttgtttgt ctgtttgttt 6600
ttttgagaca gagtcttgct ctgttaccca ggctggagtg cagtggcaca atcttggctc 6660
actgcaagtt ctgcctcccg agttcatgcc attctcctgc ctcagcccct cccaagtagc 6720
tgggactaca ggcacccgcc accacgcctg gctaattttt tgtatttttg gtagagatgg 6780
ggtttcacca tattagccag gatggtctcg atctcctgac ctcgtgatct gcccacctcg 6840
gcctcccaaa ttgctgggat tacaggcatg agccactgcg cccagcctaa aatgtttttt 6900
ttacataatg ggtgttcagc acatgttaaa gccttctctc catccttctt cccttttgtt 6960
tcatgggttg actgatctgt ctctagtgct gtacttttaa agcttctaca gttctgaatt 7020
caaaattatc ttctcactgg gccccggtgt tatctcattc ttttttctcc tctgtaagtt 7080
gacatgtgat gtgggaacaa aggggataaa gtcattattt tgtgctaaaa tcgtaattgg 7140
agaggacctc ctgttagctg ggctttcttc tatttattgt ggtggttact ggagttcctt 7200
cttctagttt taggatatat atatatattt ttttctttcc ctgaagatat aataatatat 7260
atacttctga agattgagat ttttaaatta gttgtattga aaactagcta atcagcaatt 7320
taaggctagc ttgagactta tgtcttgaat ttgtttttgt ag 7362
<210> 53
<211> 1431
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> constructs
<400> 53
gaattcgcgg ccgcttctag aggtttgggg ccagagtggg cgaggcgcgg aggtctggcc 60
tataaagtag tcgcggagac ggggtgctgg tttgcgtcgt agtctcctgc agcgtctggg 120
gtttccgttg cagtcctcgg aaccaggacc tcggcgtggc ctagcgagtt gccaccatgg 180
cgacgaaggc cgtgtgcgtg ctgaagggcg acggcccagt gcagggcatc atcaatttcg 240
agcagaagga aagtaatgga ccagtgaagg tgtggggaag cattaaagga ctgactgaag 300
gtttacacgg ctttcatgtt catgagtttg gagataatac agcaggctgt accagtgcag 360
gtcctcactt taatcctcta tccagaaaac acggtgggcc aaaggatgaa gagaggcatg 420
ttggagactt gggcaatgtg actgctgaca aagatggtgt ggccgatgtg tctattgaag 480
attctgtgat ctcactctca ggagaccatt gcatcattgg ccgcacactg gtggtccatg 540
aaaaagcaga tgacttgggc aaaggtggaa atgaagaaag tacaaagaca ggaaacgctg 600
gaagtcgttt ggcttgtggt gtaattggga tcgcccaata aacattccct tggatgtagt 660
ctgaggcccc ttaactcatc tgttatcctg ctagctgtag aaatgtatcc tgataaacat 720
taaacactgt aatcttaaaa gtgtaattgt gtgacttttt cagagttgct ttaaagtacc 780
tgtagtgaga aactgattta tgatcacttg gaagatttgt atagttttat aaaactcagt 840
taaaatgtct gtttcaatga cctgtatttt gccagactta aatcacagat gggtattaaa 900
cttgtcagaa tttctttgtc attcaagcct gtgaataaaa accctgtatg gcacttatta 960
tgaggctatt aaaagaatcc aaattcaaac taaaaacttg tttattgcag cttataatgg 1020
ttacaaataa agcaatagca tcacaaattt cacaaataaa gcattttttt cactgcattc 1080
tagttgtggt ttgtccaaac tcatcaatgt atcttatcat gtctggatca agcttgaggg 1140
cctatttccc atgattcctt catatttgca tatacgatac aaggctgtta gagagataat 1200
tggaattaat ttgactgtaa acacaaagat attagtacaa aatacgtgac gtagaaagta 1260
ataatttctt gggtagtttg cagttttaaa attatgtttt aaaatggact atcatatgct 1320
taccgtaact tgaaagtatt tcgatttctt ggctttatat atcttgtgga aaggacgaaa 1380
caccgcagcg ctgacaacag tacttcaaga gagtactgtt gtcagcgctg c 1431
<210> 54
<211> 1437
<212> DNA
<213> Artificial Sequence (Artificial Sequence)
<220>
<223> constructs
<400> 54
gaattcgcgg ccgcttctag aggtttgggg ccagagtggg cgaggcgcgg aggtctggcc 60
tataaagtag tcgcggagac ggggtgctgg tttgcgtcgt agtctcctgc agcgtctggg 120
gtttccgttg cagtcctcgg aaccaggacc tcggcgtggc ctagcgagtt gccaccatgg 180
cgacgaaggc cgtgtgcgtg ctgaagggcg acggcccagt gcagggcatc atcaatttcg 240
agcagaagga aagtaatgga ccagtgaagg tgtggggaag cattaaagga ctgactgaag 300
gcctgcatgg attccatgtt catgagtttg gagataatac agcaggctgt accagtgcag 360
gtcctcactt taatcctcta tccagaaaac acggtgggcc aaaggatgaa gagaggcatg 420
ttggagactt gggcaatgtg actgctgaca aagatggtgt ggccgatgtg tctattgaag 480
attctgtgat ctcactctca ggagaccatt gcatcattgg ccgcacactg gtggtccatg 540
aaaaagcaga tgacttgggc aaaggtggaa atgaagaaag tacaaagaca ggaaacgctg 600
gaagtcgttt ggcttgtggt gtaattggga tcgcccaata aacattccct tggatgtagt 660
ctgaggcccc ttaactcatc tgttatcctg ctagctgtag aaatgtatcc tgataaacat 720
taaacactgt aatcttaaaa gtgtaattgt gtgacttttt cagagttgct ttaaagtacc 780
tgtagtgaga aactgattta tgatcacttg gaagatttgt atagttttat aaaactcagt 840
taaaatgtct gtttcaatga cctgtatttt gccagactta aatcacagat gggtattaaa 900
cttgtcagaa tttctttgtc attcaagcct gtgaataaaa accctgtatg gcacttatta 960
tgaggctatt aaaagaatcc aaattcaaac taaaaacttg tttattgcag cttataatgg 1020
ttacaaataa agcaatagca tcacaaattt cacaaataaa gcattttttt cactgcattc 1080
tagttgtggt ttgtccaaac tcatcaatgt atcttatcat gtctggatca agcttgaggg 1140
cctatttccc atgattcctt catatttgca tatacgatac aaggctgtta gagagataat 1200
tggaattaat ttgactgtaa acacaaagat attagtacaa aatacgtgac gtagaaagta 1260
ataatttctt gggtagtttg cagttttaaa attatgtttt aaaatggact atcatatgct 1320
taccgtaact tgaaagtatt tcgatttctt ggctttatat atcttgtgga aaggacgaaa 1380
caccggcctg catggattcc atgttcaaga gacatggaat ccatgcaggc ctttttt 1437
<210> 55
<211> 113063
<212> DNA
<213> Intelligent (Homo sapiens)
<400> 55
ggcgacgacc agaaggggcc caagagaggg ggcgagcgac cgagcgccgc gacgcggaag 60
tgaggtgcgt gcgggctgca gcgcagaccc cggcccggcc cctccgagag cgtcctgggc 120
gctccctcac gccttgcctt caagccttct gcctttccac cctcgtgagc ggagaactgg 180
gagtggccat tcgacgacag gttagcgggt ttgcctccca ctcccccagc ctcgcgtcgc 240
cggctcacag cggcctcctc tggggacagt cccccccggg tgccgcctcc gcccttcctg 300
tgcgctcctt ttccttcttc tttcctatta aatattattt gggaattgtt taaatttttt 360
ttttaaaaaa agagagaggc ggggaggagt cggagttgtg gagaagcaga gggactcagg 420
taagtacctg tggatctaaa cgggcgtctt tggaaatcct ggagaacgcc ggatgggaga 480
cgaatggtcg tgggcaccgg gagggggtgg tgctgccatg aggacccgct gggccaggtc 540
tctgggaggt gagtacttgt ccctttgggg agcctaagga aagagacttg acctggcttt 600
cgtcctgctt ctgatattcc cttctccaca agggctgaga gattaggctg cttctccggg 660
atccgctttt ccccgggaaa cgcgaggatg ctccatggag cgtgagcatc caacttttct 720
ctcacataaa atctgtctgc ccgctctctt ggtttttctc tgtaaagtaa gcaagctgcg 780
tttggcaaat aatgaaatgg aagtgcaagg aggccaagtc aacaggtggt aacgggttaa 840
caagtgctgg cgcggggtcc gctagggtgg aggctgagaa cgccccctcg ggtggctggc 900
gcggggttgg agacggcccg cgagtgtgag cggcgcctgc tcagggtaga tagctgaggg 960
cgggggtgga tgttggatgg attagaacca tcacacttgg gcctgctgtt tgcctgagtt 1020
tgaaccacac cccgagtgag cagttagttc tgttgcctac gcctttccac catcaacctg 1080
ttagccttct tctgggattc atgttaagga tacccctgac cctaagcctc cagcttccat 1140
gcttctaact catactgtta ccctttagac cccgggaatt taaaaaaggg gttaatcttt 1200
tcatgcaact ccacttctga aatgcagtaa taacaactca gaggattcat cctaatccgt 1260
ggttaggtgg ctagactttt actagccaag atggatggga gatgctaaat ttttaatgcc 1320
agagctaaaa atgtctgctt tgtccaatgg ttaaatgagt gtacacttaa aagagtctca 1380
cactttggag ggtttctcat gatttttcag tgttttttgt ttatttttcc ccgaaagttc 1440
tcattcaaag tgtattttat gttttccagt gtggtgtaaa ggaattcatt agccatggat 1500
gtattcatga aaggactttc aaaggccaag gagggagttg tggctgctgc tgagaaaacc 1560
aaacagggtg tggcagaagc agcaggaaag acaaaagagg gtgttctcta tgtaggtagg 1620
taaaccccaa atgtcagttt ggtgcttgtt catgagtgat gggttaggat aatcaatact 1680
ctaaatgctg gtagttctct ctcttgattc atttttgcat cattgcttgt caaaaaggtg 1740
gactgagtca gaggtatgtg taggtaggtg aatgtgaacg tgtgtatttg agctaatagt 1800
aaaaaatgcg actgtttgct tttccagatt tttaattttg ccctaatatt tatgactttt 1860
taaaaatgaa tgtttctgta cctacataat tctatttcag agaacagttt taaaaactca 1920
tagtctttta aaaaataatc aagaatattc ttaagaatca aaatcattga tggatctgtg 1980
atttctttta ccatcatgaa aaatgtttgt caattttaat ccattctgat ttttaaaata 2040
tgactttgat atgcccctgt gatgtgtata aagagaccta tttgtggccc taaaatggaa 2100
agaacagatt agtctttgat agagttactt catgtgatca tttggtctct gtgaacactg 2160
aggacagaga aaagtgcttg agggctgcta ctaatctctc agaaacattt gtatagttca 2220
tccatcaaat gacacacata ctaaaagaat aaagaaattg atgcttatta cctacttgtt 2280
cctaaagttc caccttgggg tatacaccca aactctgact ctcttttctg taacttgaac 2340
tgtattcaat tgagtgttat tttacaaacc actttgaatt ccttggaaaa gaatagacac 2400
acactctcat ccacaggcat agacacacac actcaacaca gacacattgc ccattcttcc 2460
tctcttcttt ctcctctgag ctttttcaca ttctctggtg gcaactatag cagtaagagt 2520
cacaggatga acagtcaggt ggaggatgac cacattgagt tgcctagctg aaacatgtgc 2580
tccgtctatg tctgcaaagt gaaagaaagc tacactatct cttcaacata gatcagtggg 2640
ggaaatttta tacttgggat gatttatatg aatgcatctc atcaaagttc acaacacatt 2700
tttttttcag ttttttattt tcagttttta gagtcagggc cttgctctgt cgcccaggct 2760
ggactgcagt gatgctatca tagctcactg catccttgaa ttcctgggct caagtcatgc 2820
ccccacctca gcctcctgag tagccaggat tataggcatg tgccactgcc tcattattta 2880
gacttttctt atgttgactt aatcttccca caaatcttca attaaattac tttttttcta 2940
ccttaaaaca tattttcaga aagtcattga aatagggtgt tacaagagga aaaaattgat 3000
gagttaattt taaatatttt atgaagtgtg aattatacct ttttagatgg aatttggaat 3060
actgaatcag tgacatgcag tttatcaata tctttccgtt tgtcctcaga tttccaagtt 3120
ctgcaagcac aagtttcttt gacttagtta ccttttaact gttcattgaa atcattttca 3180
atgtctctca tggcatttaa cacatagcac attctataaa ttttttattg gttacattct 3240
gagttctaat tgagagttga acttacacac agaatttaag ataaaaaatg accatgtgaa 3300
gacacaatag tatagtccag ggattggcaa aattttgggt aaggaatcag atagcacgta 3360
ttttaagcca tgagatctat gtcttggcca ggtgccgtgg ctcaggtctt taatcccagc 3420
actttgagag cccgaggctg gtggatcact tgagcccagg ggtttgagac cagcctgggc 3480
cacatggtga aaccctgtgt ctacaaacaa cgcaaaaatt agccgggtat ggtagcatgc 3540
atgtgtattg ccagctaccc aggaggctga ggtaggagga tggcttgagc catacagctc 3600
actgcagagg ttgcagtgag ctgagatcga gccactgcac tccagcctgg gtggcagagt 3660
gataccctgt ctaaaaaaaa gaaaaaaaaa tctatgtctc aattctgctg ttgaagtgtg 3720
aaggtagtca taaacaataa ctagtgtggc tgtgtcccaa taaaacttca tttatcaaaa 3780
caggtggtgg gctggaattg tcttgtatgt tgtagcttgc tgactactga tagagtggaa 3840
agaacatgca ctaatcacac aaaccaaagt tttagttgag actacatcac ttatcacctt 3900
tagggtcttg gggaagcgta cttaacatct ctgagcatca cttccctgat tagtaaaaaa 3960
tatgatttag aaaactgcaa ctaccttgca gtttttgtgg gaatgtcata ataagacagg 4020
acatatgaat aattgagcac acttttatat ataggaacca tggttattat tatcaaataa 4080
actctccaac ggaataatta ctttgccaac acgttttcca tttattcttt tatccttcat 4140
tacataacta gtttgaaaga ttggaggcga ccaaagacca ttttataatt tcacttatgg 4200
ctgaagatgt ttggtagaag cctcataaga aaagtaatct cattccttta taagaatata 4260
cttttaacaa ctacttttta actcattgaa gaactacctt aatgatcagt gttattttta 4320
tgggttttgt tccctccatt tttgttatct gcgtacacca attttcaatc aacatacttc 4380
aatttaatag acaaaaattt cttcaaatga ctcagaaatt aattagatct aaatccaaaa 4440
gcagaaagat ttaattatct ttatataatg ctcagtaata taaatgcaat aaatacaaga 4500
aaatgatgat ctttgagtgt cttccaatgc cactctgctc aataagcagc agtggccatc 4560
agtgaaattg atagcaaatt ctcaagtcaa aatgtgcttc acctcactaa gctgacaaag 4620
tcaacataac atgcacaaca gggataactg agttctcaaa actctcaggt attacttctg 4680
accttcttct ccactctgtg ctcttttgag gttgggaaga caagataggg tgtgtgtggg 4740
acacctccgc tcagggaagc catcagctct ggtgtcccta cagcatttat accttgctag 4800
tcacataacc acttggcacc tattttgtag gtgtacgtta tcaattacag attactcata 4860
aattaaaggc taaccatcaa ttacagatta ttagtaaata attatgacct caaagaacaa 4920
ctgattggtt tgatacatgg taaccttatg aggactctca tttatctcgt ttttttaagt 4980
tatataccta tctctttggg gttgcactac aaaaatataa aatatgttgc ataagatatt 5040
tataaaaaat aattaattat aagttctaat ggtgtggttt agtggcattc tttttttttt 5100
ctttttttct gagatagggt ctcaatctgt catttcactc caggctgaag tgcagtggtg 5160
tgatctcggc tcactgcaac ctccgcctcc tgggttcaag ttattctcct gactcagcct 5220
cctgagtagc tgaaattaca ggcatgcacc accatgcccg gctaattttt gtatttttag 5280
tagagatggg gtttcaccat gttagccagg atggtctcga actcctgatc tcatcatccc 5340
cgacctcggc ctcccaaaat gctgggatta caggcgtgag ccattgcacc cggcctagtg 5400
gcattctttt ttaaaaataa atttaattgt gtatatttag ggtatgcaac atgatgctat 5460
cagatacatt agacactaaa aaattactat attgaagcaa attaatatat tcataatctc 5520
tcatagttac cttttttgtt gtttttgtgg caagggcagc taaaatccac ttatttatca 5580
tgaatctcaa atatagtaca attttatcac ctacagtcct catacattag atctgtacac 5640
tttttcatct tacacatctg ctacttgctt ggatcctatg gcctatatgt ccctattttc 5700
tacctacttt tccaccccta ttaaccctgt tttttacgta gtctctgtat atttgaattt 5760
tgtttcaagc ttccacatat atgtgagata atgtaatatt tttctttctg tgtttggctt 5820
atttcactta gcataatttt gtctgggttc atccatgttg taaatggtag gatcttgttt 5880
ttttagggct gactgatatt ccattgtatc tatgtaccac aatcttttta tctacctatc 5940
tatcagtaga cactttagtt gtggctatta tgtttttctt tttttctttt ttggagacag 6000
ggtcttgctg tcacccaggc tgcaatggag tggtgttatc atagctcact gtaacctcaa 6060
acttctgggc tcaagagatc ctcctgcctt ggcctcccaa gtagctgaga ctacaggcat 6120
acattaccat gcctggctaa tttttaatat tttttgtaga tatagcatct cactctgttg 6180
cccagactgg tctcaaactc ctaattcaaa tttagaatag agtatgacaa ttctgtaaaa 6240
tataaaaaac atgtccactc cgtataggaa gttatacaat gagaagaaga caaacactat 6300
ttacattact cttgataagt tttttacaaa gaaataaaac actttaattt ctaatgtttt 6360
aaattctggt ttgctaaata aataaatatt agttttagtg tttttaaaat tccttatata 6420
gttataagtg atcttcctgc ctcagcctcc caaagcactg ggattccaag caagagccac 6480
tgtgttgggg cccttggaaa cagatatgct gaaatctttt cttgtggatc tacacccaga 6540
agagggattg ctgggtcata tgctactcta tttttaattt ttcttttatt tttagtgaat 6600
atgtaataat tgtatataat tgtgggatcc agaattatat ttccatacat gtatacaatg 6660
tgtgataatc aaattagggt aattaacata tccattacct gaaacattta tcattccttt 6720
gtggtgggaa cagtaaaaat taaaaattct ctcttctaga tttttgaaca tatgcaataa 6780
actattgtta agtatatcac cctacagtac tacagaatgc tagaactcat tcctcatatt 6840
tggctccaat ttcatattct ttaaccaacc tctccatatc ctcccctccc tcttaccgtt 6900
gtcagcctct aataatcata attctactct ctacttctat ctcattgtct ttgatttaga 6960
atatgtttca taatttaacc aaaggtcaaa ttcttaggta ctgctaaggc aaagaacaaa 7020
gatcgcattc cagctgttag acatttctta ctactagtca tttttaagac aacatggggt 7080
gcaggtggtg aggatgagag atagagattg aaacatattc tcttaaatat cagctgttct 7140
cactctgcat agttccagca caaacaaatt ccaggtacta tggttagtta aataacacca 7200
gccactaaca acacaattca aatttctgtt accacagtat accgaaagtc attgcataaa 7260
gtacaaactt tgctgctaac tcttcagcct tcaaatcatt acataaataa cagaaaccca 7320
ttataatcag tgacaaaacc acagcacttc tttcaaagct ttttggagat tggttgcttc 7380
acatctgtta tgcagttcat acagacagca atgcccggac ttgtgtggcc acattgtctc 7440
ccagtggtga gcccatgtga tgtttcacga aaatgcgcaa tcaaaagagg aaactggcca 7500
gcaaagatga aagagtagca aacaaaggaa gtgaaacatt ctggaagtaa aatttgaatc 7560
aaacataagt tgatgtatac aggaagtagc taccctgagg atgttgtcac tgctgcaatt 7620
caggagactc taaatatgca gtcagaggaa cgtagtgagg tgaaggtatc cgtataatgg 7680
ggaaagaggt tgtgataaag agtgaaggtg tcccagagga agtgttgctg aaaaatacac 7740
cttatgttaa atacactgtc agtatatcat gacattaaag tgcaaatgat aacattttgt 7800
aaactgatcc aaacttaaaa aggagtatga taattctgta aaacataaaa atcatgccga 7860
ttccataaat tatacagtgt gaattacact gaaaaatcca acattagaga ggatatgaat 7920
acaatttttt acaagcataa ttttaataat acacataata attatttgta ttcaagttta 7980
gtaatgttca aggtttggaa gaaattctga tcctgtgtag agaccctagt ttgaatgtgc 8040
ttatagccta ttattacatg tgtaatgtta cataaattac ttaactcgga tttttaattt 8100
catcagctat ttaaaatggg cataatataa ctatattaaa tggctgttat gaagattaaa 8160
taagatgata tgtaaaatgt gttttttgtt tgtttgtttg tttgtctgtt tgtttttttg 8220
agacagagtc ttgctctgtt acccaggctg gagtgcagtg gcacaatctt ggctcactgc 8280
aagttctgcc tcccgagttc atgccattct cctgcctcag cccctcccaa gtagctggga 8340
ctacaggcac ccgccaccac gcctggctaa ttttttgtat ttttggtaga gatggggttt 8400
caccatatta gccaggatgg tctcgatctc ctgacctcgt gatctgccca cctcggcctc 8460
ccaaattgct gggattacag gcatgagcca ctgcgcccag cctaaaatgt tttttttaca 8520
taatgggtgt tcagcacatg ttaaagcctt ctctccatcc ttcttccctt ttgtttcatg 8580
ggttgactga tctgtctcta gtgctgtact tttaaagctt ctacagttct gaattcaaaa 8640
ttatcttctc actgggcccc ggtgttatct cattcttttt tctcctctgt aagttgacat 8700
gtgatgtggg aacaaagggg ataaagtcat tattttgtgc taaaatcgta attggagagg 8760
acctcctgtt agctgggctt tcttctattt attgtggtgg ttactggagt tccttcttct 8820
agttttagga tatatatata tatttttttc tttccctgaa gatataataa tatatatact 8880
tctgaagatt gagattttta aattagttgt attgaaaact agctaatcag caatttaagg 8940
ctagcttgag acttatgtct tgaatttgtt tttgtaggct ccaaaaccaa ggagggagtg 9000
gtgcatggtg tggcaacagg taagctccat tgtgcttata tccaaagatg atatttaaag 9060
tatctagtga ttagtgtggc ccagtattca agattcctat gaaattgtaa aacaatcact 9120
gagcattcta agaacatatc agtcttattg aaactgaatt ctttataaag tatttttaaa 9180
taggtaaata ttgattataa ataaaaaata tacttgccaa gaataatgag ggctttgaat 9240
tgataagcta tgtttaattt atagtaagtg ggcatttaaa tattctgacc aaaaatgtat 9300
tgacaaactg ctgacaaaaa taaaatgtga atattgccat aattttaaaa aaagtaaaat 9360
ttctgttgat tacagtaaaa tattttgacc ttaaattatg ttgattacaa tattcctttg 9420
ataattcaga gtgcatttca ggaaacaccc ttggacagtc agtaaaatgt ttattgtatt 9480
tatctttgta ttgttatggt atagctattt gtacaaatat tattgtgcaa ttattacatt 9540
tctgattata ttattcattt ggcctaaatt taccgagaat ttgaacaagt caattaggtt 9600
tacaatcaag aaatatcaaa aatgatgaaa aggatgataa tcatcatcag atgttgagga 9660
agatgaggat gagagtgcca gaaatagaga aatcaaagga gaaccaaaat ttaacaaatt 9720
aaaagcccac agacttgctg taattaagtt ttctgttgta agtactccac gtttcctggc 9780
agatgtggtg aagcaaaaga tataatcaga aatataattt atataatcgg aaagcattaa 9840
acacaatagt gcctatacaa ataaaatgtt cctatcactg acttctaaaa tggaaatgag 9900
gacaatgata tgggaatctt aatacagtgt tgtggatatg actaaaaaca caggagtcag 9960
atcttcttgg ttcaacttcc tgcttactcc ttaccagctg tgtgtttttt gcaagattct 10020
tcacctctgt gtgatttagc ttcctcatct ataaaataat tcagtgaatt aatgtacaca 10080
aaacatctgg aaaacaaaag caaacaatat gtattttata agtgttactt atagttttat 10140
agtgaacttt cttgtgcaac atttttacaa ctagtggaga aaaatatttc tttaaatgaa 10200
tacttttgat ttaaaaatca gagtgtaaaa ataaaacaga ctcctttgaa actagttctg 10260
ttagaagtta attgtgcacc tttaatgggc tctgttgcaa tccaacagag aagtagttaa 10320
gtaagtggac tatgatgcct tctagggacc tcctataaat atgatattgt gaagcatgat 10380
tataataaga actagataac agacaggtgg agactccact atctgaagac ggtcaaccta 10440
gatgaatggt gttccattta gtagttgagg aagaacccat gaggtttaga aagcagacaa 10500
gcatgtggca agttctggag tcagtggtaa aaattaaaga acccaactat tactgtcacc 10560
tgatgatcta atggagactg tggagatggg ctgcattttt ttagtctttt ccagaatgcc 10620
aaaatgtaaa cacatatctg tgtgtgtgtg tgtgtgtgtg tgtgtgtgcg tgtgtgtgag 10680
agagagagag agactgaagt ttgtacaatt agacatttta taaaatgttt tctgaaggac 10740
agtggctcac aatcttaagt ttctaacatt gtacaatgtt gggagacttt gtatacttta 10800
ttttctcttt agcgtattaa ggaatctgag atgtcctaca gtaaagaaat ttgcattaca 10860
tagttaaaat cagggttatt caaacttttt gattattgaa aactttcttc attagttact 10920
agggttgaat gaaactagtg ttccacagaa aactatggga aatgttgcta ggcagtaagg 10980
acatggtgat ttcagcatgt gcaatattta cagcgattgc acccatggac caccctggca 11040
gtagtgaaat aaccaaaaat gctgtcataa ctagtatggc tatgagaaac acattgggat 11100
aaatcggctg ctatcataat cattcctctc ccacatcaga taaatgaatt aactttttga 11160
atagggttat ttaatataaa gtgcttaagt ctaattatga gaagaaataa gataattaca 11220
cttcaatggt taaagagagg gagaataatt tgcatattat gcctgatgta aaatgtttat 11280
tatgggtaca tattaagtgc taactaattg ttaattgttc ttgctacaag tcttaatgca 11340
gggaaacaag aaattattac atagtaccta atattatctt ctaatattaa agaaacaatt 11400
tcccctaaat tcatcccatt agcttttttt ttttcggtgg ggcaggggag aaatacagac 11460
ttcagtaaac ttgggctggg aactttctac ctacaaagtt caaataaaat aaattatcct 11520
agttagataa tatcaatgaa aaatccacca acttaaatcc tggctgtttg atctcaggaa 11580
attatttcag ttatcaactt aatgcatcat attatagaaa tatatgaaaa tgtgtttaat 11640
taaacttact gaatgatatg ttttttcagg tactttaaaa ataaactatg atataaagtt 11700
acctattttt catgcaagta tagtataaag aaatttctaa cactggagat tttctgaagg 11760
ttttgattct tataaattta ttacatcata atgaacaaaa ctaattttca acatattatg 11820
atttaaattt ccttagtaaa ttgtttcaaa tttattttct ttaaatccat atttacatat 11880
gtatatttaa atatacatat ttacttgtat aacaattcaa aaccatatat taattttata 11940
attttgttta atgtcaaagg ttagatttgg ctatatctat tctaaaagtt ggtatcacat 12000
ttcctttttg gaattttatt tttaaagtag ctaaagtcaa atataaacct attatttata 12060
ttaatgcaga cattagaggt agacactaaa ttcattttag tatattctaa attatttatt 12120
atctactatg aaataatata aagaaaaata aagcagaatc cctgatttca aagaactcaa 12180
ttgccgaaaa acagttacca tttattagac ccaaaatgta ctaatatgag tgtgtctctt 12240
ttccttttgt tttgtcaccc gtcatttgga atgtcagtga gtagagagat agtgtgaaag 12300
gccctcaagg ggaaaaatag aggttaaagg tcagcagaga ccctactaga gaaatcagtt 12360
ctacagaaat gtttttaaat gtgtcgatta ttgctacatg tacactctgt cattttgtaa 12420
tgtagccatt ttatttatga ttataataat aaaacaacaa aattataata atgtgtagag 12480
tacattttac tgtgcagtgt attgcattaa aactagatta aaatttatac atatataaaa 12540
ggctatctag atattataaa atttatggct ggatctgtaa aaaattcaaa acctattttt 12600
aatctcgctt tgagatttta taacaagaaa atgttcgttt caagcaaaat tttcaattca 12660
cgtccttgaa aaggaaaaaa atgacaactt gaaacacata attgactatt tttaaaggat 12720
caacatttca gaaatgtttt aaaacataag attttcagta cagcttttcg ctggcattta 12780
aatcgaactt tgaattgtaa atagctcttg ctcttaagga gacatcagcc atatccttag 12840
aagtggcacg gagttgttag gtagttgtac aaaattctag cctaaaagac aaatagggag 12900
caacactact gtggaccgtt tctggtcttg ggctgtgtgg ctatgtcagg cttgcccaca 12960
ttgcctgtac taaggagaaa gcctcttgtc cttacagacc cccttagctt acatagtcta 13020
tttgaaaaca aattgctttg tccacaccat ttaaatattg gcttcaggcc aggcgcggtg 13080
gctcacgcct gttatcccag cactttggga ggctgaggcg ggcagatcac gaggtcagga 13140
gatcgagacc atcctggcta acacggtgaa accctgtctc tactaaaaat ataaaaaaat 13200
tagccgggtg tggtggcgcg cacctgtagt cccagctgct ggggaggctg aggcaggaga 13260
atggcctgaa cccgggagtc ggagtttgca gtgagccgac atcgtgccac tgcactccag 13320
cctgggtgac agagcaagac tccgtctcaa aataaataaa taaataaata aataagtaaa 13380
tattggcttc ttcaactggt gagatgaaac ctatacaata gtcatgtgaa tagcactaaa 13440
cagctgacat ggtgtaactc ctctcagact gaggcttatc tggggagtac aaagcatgtc 13500
aagaaaatgt gccttcattt ccttagatga gtgtccccat cctccactct cctccactgt 13560
tctcctctct gcttctatga tatcaacttt tctttttctt tagattccac atgagtgaga 13620
tcatgtggtt gtttgccttt ctgtttctgg cttatttaac tgaacaagaa agtttttgac 13680
atgaaattaa acttctgctt gtaaactcaa ttcaaactat ttacactgtc ttctcaaaaa 13740
tgttaactta ttttaataaa tctactgaat gaccgtatct cattttgttt tatgaaaaga 13800
aattgtaagg gtgctcaata gcctcttcat tttcatactg tctagctcct gtgctcctat 13860
taaaattact gcaaatttag ctttttaaga accctttgtt tcactacctg aagttctata 13920
aaaagatcca agttccttca caaccgtttc ttatgctgtt attcgtacat atgtgataat 13980
accacgtctg aacacgtaga taataagtag gggctgggtg cggtggatca tgcctataat 14040
cctagcactt tgggaggcta aggcgggtgg atcacctgag gttaggagtt cgagaccggc 14100
ctggccaaca tgatgaaacc ctgtttctac taaaaataca aataataata ataataataa 14160
ttagccaggt gtggttgtgg gcacctgtaa tcccagctac tcgggagact gaggcaggag 14220
aatagcttga actcaggagg cggaggttgc tgtgagctga gattgtgcca ttgcattcca 14280
gcctgaacaa caagaatgaa actccatctc aaataaataa ataaatagaa gtatgtattg 14340
tgttgcttag aaggtgtggt ggaaattaac ttgctgagtg agatcaaagg attggcactg 14400
aattgaaata aagaaatatt catgctgagt ctggttcaaa tataactgca cctgtaagaa 14460
ttgctttctg taaactttcc atagtataaa ccaaatccaa atcactcatg gctttacatt 14520
cctgatcgtt aaacttgaag cactttttaa tactgcatga ctttagccaa aatatcttag 14580
ccaagattca atgtttggtt gaaccacact cacttggaca tcttggtggc ttttgtttct 14640
tctgaccact cagttatcta tggcatgtgt agatacaggt gtatggaagc cgatggctag 14700
tggaagtgga atgattttaa gtcactgtta ttctaccacc ctttaatctg ttgttgctct 14760
ttatttgtac cagtggctga gaagaccaaa gagcaagtga caaatgttgg aggagcagtg 14820
gtgacgggtg tgacagcagt agcccagaag acagtggagg gagcagggag cattgcagca 14880
gccactggct ttgtcaaaaa ggaccagttg ggcaaggtat ggctgtgtac gttttgtgtt 14940
acatttataa gctggtgaga ttacggttca ttttcatgtg aggcctggag gcaggagcaa 15000
gatacttact gtggggaacg gctacctgac cctccccttg tgaaaaagtg ctacctttat 15060
attggtcttg cttgtttcag gcattaaccc agataaatgc catgcaaatt ttataattat 15120
tatgattgtt tcaatttctg gaagaaagtt aatgaaacaa aaaatgtagt aaaatgccaa 15180
aggaacagtg acatttcaga aagaatgagg gctttcatgt taattgtaag tcttggaatt 15240
tctcttcctt ggagtaacaa atccctttgt gcctaatttc ctaatttcca aaataaagtt 15300
cttttactta tttctttata gtgacatcat ctcttattaa atggcatatc tgcatattac 15360
ataacagttc attgccaaat acatatttgt gggaaatgag agacttaaaa tacataccaa 15420
ccagagatat agttttgagg tagattttaa aattctgaga agaattttga ctgaattttt 15480
ttgacaaaca tgggacacga ataagattat accaaagata ttataacttt cattttaaat 15540
atggaactaa tacagtatga ggtgtcaaca acgttgaagt ttcacaaaca tcaccactac 15600
aacagcaaaa taatttttgc tttttccctg ccacaatgac ctccttgcta tttcttgaat 15660
aaatcaagca tacccttgcc ctgacacgtt cttggggagg cctgccctaa tctatataaa 15720
attggagcca ttcttctcac ctctggtatt cccagtctcc ctactttttt tccttctttc 15780
tttctttttc tttttctttc tttctttcct tctttctctc tttcctttct ttcttttccc 15840
ttccttcctt cctttctccc ttccttcctt cctccctctc tccctccctt ccttcctccc 15900
tttctttctt tctctttttt ctttcttgct tccttccttc cttctttcct tttctttctt 15960
tttcctttct ttgccaaagt gttattcacc tttaaatata atacataatg tgcttacttt 16020
aatgtatgat ttttatttta tttctccctt ctagaatgta ggcaccatga gagtgaaata 16080
tatttatttt gttcattgat atttcacaag tgtctgggag agtttccaac ttacagtaga 16140
caattaacaa acatttatta aattaaggag ggaaggaagt gagtaagcac aacaactttc 16200
atttctgggt cttttataat catatgctta gtataagaac agtgctattc agctatccaa 16260
aagttacaat caaaatgatt ttggatgaat atcttgaaaa ttgtgagaaa gaagttttat 16320
ttgctggcaa actattctgg gttgtttcca cttcatgtaa tcctaagtag cagccttacc 16380
ttgatagccc attaaaactc tgataataaa aaggcagaac aaaaatatct gtgatatatt 16440
tagatttact acatgtactt acatgtctag tgtctggtgc aatggatgct aatgatggca 16500
aatccttact gggcttctag tgaagttctt cagctaatgt ttgaatgcat ggttggtcat 16560
ggtggtaccc ctttgtacaa aatatgcttt tcaaataatc ttattaggga taataattat 16620
attaattcct ggtttccatc taaaatttta attctattta tagcttcgta agatttcaca 16680
agttaagagg gacctcagat taaattagta cacaggcaat taatcagttt tgtgtctccg 16740
acccttttca cgggctaata gaagctatag accctcttag cttcagaaaa atgcgcactc 16800
acatacgcac atcaaagagc ttaatgggaa gtccattgac agaccctctg ttcagatcaa 16860
tcttctgatt gtagagatga ggaaacagaa atctacagag gaagtgggta gtccaagatt 16920
gcacagtcat ttggaataga ctggacacca gtagtacttt tccagccact atatcacttc 16980
cccaagcact tcctcaaaac ttaccttcct ttgggtcttt atacattcag ttatggacaa 17040
ctagatttaa ctagaggatt ttattgcttc agaatattaa gcaacaggga aacatgtacc 17100
gtcttttatt cacctgcatt taaggcatac aatataaatt gcaaatggag catgaaagtg 17160
cttaatcttt tacaaaactg ggtttgcttt ccacccatct aaaaatactt ctatttattt 17220
taatatttaa agcagaaatc taagtgatgt gacaaaatta atcatttgga gatatttccc 17280
ttataggtag tatagtttct tactgatttc taatatgaaa atgaagccat agaacctaga 17340
aattgcagca tagttgtgga aataaacatt ggactgagag tgaaaatggc tagtcttcct 17400
ctctgctcat acaccacctg actggataac ctttcgcaga tctcctaaaa gtctttctca 17460
taaaatgagg aagctctact agaaaattgt tgaagtctaa tttagcaata aagttctgag 17520
tttctataat aattcaaaga atactctaat aaatgtctgc aattgtggtc acatctatgg 17580
gatgctaaaa aatctggatg gtttcaatga aagtatttaa tttgttcatt atgaactttg 17640
aaataattta tttcattttt taaactttga tcaaaatgac cctggtaaat agaaataagc 17700
aaactctttt tgcttgaaat gcttattaat gactgcattg agacactcat tcatcattca 17760
agaaagaatg tttgctcaca ctgtgccaga aacttggagg aagagggatg tgacaagtag 17820
gggtactgga tgtctagctt gtagaagtgg attaatggct ctgcttttaa gatcaggaac 17880
actgaaaggg agtaatggca ccggttttca cctttcatgc cctttgaggg tatctggtcc 17940
atcaccctct agttgatgag ggagggaaag ttccctctcc cttcacaaat aggtggaaat 18000
taaatgacat aattctgaac aaccaataaa tcgagagtaa atcaaagcag atacctgttt 18060
tgttaatttg atcatatgaa tgtagctgcc cttagtaata atttctaagt ataagactag 18120
ttaaaggaca aatgagttat cttgaattat aagattttgt tttacagaac aatattaact 18180
cttgtgttta gtacattaga ataatagatc ttttgatcca tatttttact catgtgcaca 18240
taagaagtta tcagtcatac aattcatttc ttgaagttca tacctttcat tggcagagta 18300
gaaacaggtt aaaagtgcac aggcagaaat tttaagtgca aagcaacagt gatgttatat 18360
agagaaaatt tatatttcct acttctattg aagaagaaag atctgcttgt tctaagaata 18420
ttgtacaaag aaagtgactt gaatcagcgt tattctgtaa tgctactatg cgtgcagtgt 18480
ggagtagcca ctagaacact tggtctatcc cagctcctca acagtgtctt gcttgtggct 18540
ggtgctcaaa taaatccttg ctgaactaat gagcatctct ttcatgccac atggaatgct 18600
ctaaaagagt tggatcctga agtttttata tttttgtaat tttctggagt tttagagagc 18660
aaaagtcctg aataaactgt gaagccactg cctgacaaat aatacagcag tcagcttcgt 18720
tatcatatcc cattgagaca cgacttatct acatgatgat taatagtttt cacgcaagaa 18780
ataagcttga aatgtctgtt gccttggata cttaaaacat ccaggttcag cgatgttatt 18840
tattgttgtt caaaatcaga atgaagttcc taagcaatgc cattttggaa aaattacatc 18900
aatatattat gaacaacttt ttttaaatct tgatttcaaa tggattgaca cgtgtatatt 18960
ctgtaataat cctgacttaa ttcataaaag gatagctagc cagttgtgtg ctagatgaat 19020
aaaaaaaaag caggttttaa aatgtcaggt ttgacattgt gaatataata tctaagtatc 19080
cttttactca tttcctttga cttactatgg ctgtcatgtt gggcttcatg aaaatttatt 19140
tttaaacact tgagtgttat ggaccctctg attaaatgat taatcagatg atgtatgttg 19200
ccatcagctg aatcatttaa tgttgatttc acaaacaagc acaggtcaca ggcaacattt 19260
cagatttctt tgaagaagca cacacaggtc acaggcataa tcttaaaata attttataac 19320
aaggtagtaa taagagatgt caggactgga gaaatatttt aatttatagt aagctttccc 19380
cttaagtgtc taataattgt taatataata cattgcctca aataattaaa agtttggttc 19440
ttgtccttgt gcttgacttc agaagataac cagatgacta ttaggtatat ttagacctaa 19500
attaaaagct ttgagacaca atgaattgcc tgatttgtat ttgtgtttcg agtggcatat 19560
actattactg gcactataat cttagattaa agcatactgt gattattaaa gaaaaattta 19620
agattgattt gtttctaaag gtatgtaaca gtgacatttt gcaatgtggt atgtaaaagt 19680
tggtatttct cactcatatg agagcccact aatggtacat aaactgtccc cacttagaaa 19740
cacaattatt atggcctttc tttgtatctg acaaaatttc actgggttca agatggatga 19800
atagtgaatt ctaatgaccc ttaatcctgt aaggttctag gtgggaaagt actctgtaat 19860
tatgtataaa attataagga aaataggctt actgctatgt tttcattaaa aatcattaac 19920
tgagtactta atatgtgcca gacactcagc tgggcaccat gagaaataca aaactgagta 19980
acatatgggt ggctcctgcc ttcaagaaat gggcagttca ggccgggaga ctgacatatt 20040
taccctggga aaaagggagc agctgtggtc tctgagaaca atatggtttg ttacaagtat 20100
atatccatca tggaaaaaaa gagatttatc ttagaaatga gagaggctga tgctctcaat 20160
aaatatcata cattaaattg tgtttttgtc agtagactga aattacctca catacacgca 20220
cagatagtag ccatgatatt ttagctgctt agatatagag acaaatactt ccacccaaat 20280
cttaggatca gtggttaata gtctgtaagc attacaatcc cacaacatat gcatgactat 20340
acatccaatt ttaatattca aagaactgat tgcgatgata gttttgtttg tcaaagaaat 20400
gtattatagg atgagtggga tagaactgca tcacgttaca ccaacaaata ggtttaaatc 20460
atatttgtgc acttcccttg ttccttcata aatgtttaac atagcttaaa attctgtgga 20520
ctgcaacgtg agagcaatga ccacacttct gtgaacccat ttttactgtg catgtgctaa 20580
cgtctattgt tagtattcct tcacttgcaa agatggcatg ataattttgc tggtttcatt 20640
aatgagatac tgttaaatgt aggatgactt caaacttagt tgtattgtaa aattattttt 20700
aattgtatac atttaagttg tacagcatga tgttttgaga tacttatctt tatttatata 20760
tatatataat atacacacgt atataaaagt gattcctaca ttgaagcaaa ttaacatacc 20820
catcatcata tggttatctt tgctttttta ctatcagtgc ctaaaatcta ctttcttgaa 20880
aaattaccag tatgcactac aatattatta acaataatct tcatgttgta cattagatct 20940
ttagacttac tcatcttaca tgacttaggt ttgtttttac ctctactacc atctgagcca 21000
tatttccact ttgtaatttg ataataaact tggaaaaata gcacttatat gtttaggtga 21060
cgggcataaa taggataaga tgtgtttata tattattcca tatatcttgt ctccaactac 21120
aatgataaac aacctgtttg tccctaaaaa gtaagaaata acttgacttt tctgcccctt 21180
caagcatagg ctgttagctt ttaagtttta gggagacatt gatgatgcta tttgctttat 21240
caagaggaaa ttgtcaaaag aggtcttttg gttctcaaac tattcaaagt atttaaaaat 21300
caggacaaaa tatgtttacg tgatattcaa gggtacagaa atgaggtaaa tgagatgcca 21360
attgtatttg tcatgcaaat atataattac gtgtatgaga gttagatgat acatctcatc 21420
aatttaattg ttcttctaca aggagaaaat gaacaatttg tcaactcgta tatgaagtaa 21480
tttttataag aaattttatt aaaactttta acaacatttg gatttttaag ttgcaattta 21540
aatatcccct tctaccaggt gattctggaa tcactaagca gttacttgtg aaaattccaa 21600
agtagcattt aattcttatt aatgtcatag tgaatactaa tgcaaagaat actgagccag 21660
aaattatgct tgttgaataa atagattatt tattgaacaa gtaagtgaaa aaatggaaat 21720
aaagaacgga tatatatttt atcttcctgc ttagatgtgg gactgtccta cttttctctg 21780
gtgttcacaa caacaatatg ataaatctaa ttggaattca gttcatagga atgaattcag 21840
ttacattatg gattgtgatg aataatgtac acttttaatt taatgaaatc aaatagattt 21900
taactatcta tgcttacaat ggggtgacat aagtctgaca atccttaata tcaagtcatc 21960
tccaattcac atgtatacac actttttttc tatttggcta ttgggaatcc tcacaaaaat 22020
cgaaaattgc cctttcagtg tacgttacgg tatttcatgc cacacagatt ttctgaggtt 22080
gtacatacag ctttgccttg aggttccaat ttttgctcag tggattgagt atatattatt 22140
tgctatatat cagaagaggc atgtgcttcc tacttatgtc aggtaacttt gggattaata 22200
taattgtcct acaaagcata gatagataga aatacttcat ccttaatttc taatattatg 22260
acatatctaa agtaggcacc tttaaaagtt aatctccact aaatactaat gactgcttat 22320
agtggcaatt catctttcat ggtagtcctc ctacaaaggt atactaacat ttatgagttt 22380
gaaacaaagg caattcacaa gtgttctgct agagatggtc tatatctgct gtttgatcca 22440
gcatgatggc cagctggccc tcctgtgcat gacggctcgt ggtttaactg caccattttg 22500
tttggtcata tacagggaaa acatggcatg gtgtggaggg catgggcttg aattcaggga 22560
acagagagtt ggtcttctct ctctcactct actggatgat gtcatctccc ctctctaagc 22620
atgagttttc ttatctgtga aataaaaatg ttgaattaaa tgagttcaaa atgctttcag 22680
tctgtgttta atagcttgaa tcttaagaca atgtattcaa ttatgcgttg ccagatccct 22740
ggcaactcat gtaacctttc taaaccatag ctactcatct gtaactggcc agccaactgc 22800
ccagggttgg agtgtgaatg aaataagata atgcagacaa aagattttta aaaattgtag 22860
tgcattatac agttgtaata ttttgccaag aacttacatt ttctctaaga agtgtgtcga 22920
tacatgatca cagaaaatct tttccatatt cctttgtagt ttgatgatat taagtaagta 22980
aattgtataa cacaaagagg gaaaagcatc actgaacatg ccgttttatt tagctaaata 23040
aaatgtaatc actattagtt ttcctctgat ttccccaaag tcatgtgatt ccattgagta 23100
ttatgcacat ggtataatta gaatggattc tctgctcaaa taattttggg aaacatttaa 23160
attaacaaag tttaaaagta tctctgttaa gctgaagcaa atctcaaagg ccttaatatt 23220
gtatgtaaga ggaatagtta ccatctttcc taatgcctct ttgacgccaa acccatggag 23280
aatagttcta ggtgttcagt aaaacacaga tttgggatgc cacaggttaa ttggaactgt 23340
cccctgcaat ccttttctct ttttcttaat aatggctgat tgcaggtcct agatgaaaga 23400
catttagaga gattatcagg actcagcatc ccatatcaga atccattctt ttatagtcat 23460
tttctgttac atttcttggg acaacaccaa agaaatgacc atcttcattc acataggctt 23520
tgtaccaaat gctgacaaag atccttggtg acctagatgg gggcaggtct aagtagattg 23580
cagctgtaaa attggctgat gaatgatctc agcccctttt actcacactc aaaggcagga 23640
cagtccatta aggggaagga gggcagagtt tttccttagg ccaattccct atgccagaac 23700
tttttagaat ggaagcattt ccagaggaga aacaacccca agcacagttc aaagccccct 23760
cctcccaagt tcatttgaaa gtgggatggt ttatctgcaa agggggaaaa gatgagggat 23820
agggacggga atatccctac ccttcagaga gtctggtttc atcctgcact tttactgcac 23880
agccacaaat gccttggggt gaatctacaa tatgatacat catatggtct aaacgtgcct 23940
ggctgatcct ctctaatact tcaggggtct aaaagggata acatgctctc ctgttactca 24000
ccgactctgt ccgccatatt tcacccagcc agccactgcc ttcacttccg tccgaggcct 24060
aatctgagcc catgggaaac ctaagaaccc ctaccacaac tgcctcaact cttgggaatc 24120
agggtgtatg ggggtgacag gaagtgagca tacattctcc aacttgatat gtcagccccc 24180
acgtctgtat gaatgtttgc tcacactgtg actgccggcc ttgctcctca ggctgcatcc 24240
taccagggag taagacccaa gtccttcctg ctttcagaca acaccaagcc tcatgagtcc 24300
ccactcagag gaaggaccag agacaaactc taatgttcca ctaatacttc ccttcttatt 24360
actttccttg aaaatccctt ctccctcttt ctttttatac ttcgctaatg aaaggtaatg 24420
aaagggtctg gcacttggaa tttagaattg atacatggtt tttaacccgc ggacgtattc 24480
cacaataacc cttgcatctt ctactaagat gtgggctagg aagggaccag ccagttccca 24540
gggtcacagt gcctcagctg atgtttcata ttttcagcaa ctttatgtta gagatgtcca 24600
tcaatcagaa caatatggtt agagaataaa ctaataaaag tcatttttga ggacatgttg 24660
gaagtctatc aaaagcattg aaattatgca tgctctgacc agtcgcatgt ctaagaattt 24720
aaatatgatc ataagtttaa atatgaagat gtttatcaca gaattgatta taaaacaaaa 24780
ttgaaaaaaa tagtgctaga agtttgatca tagggacctc attaaatgca ttatggttga 24840
tccatgcagt ggtttgctga acagccatta aaatgttgta gaataattat taatggtgtg 24900
gaaggatgct attgttgcag tatgtgaaaa gaacaaatta caaagcagtt tgtgcagcat 24960
aatattttta ttttttaaaa acctgtatgt ggcttatgta catataaaga cgtggaataa 25020
atgcacaagg tactcagttt ttctcagtga agcccatttt gcattttggg ctgggtaatt 25080
cttcgctgtg gagaactctc attcattgta ggatgtttac aagccctggg ccttacctct 25140
ttaacgccag taggcacccc cagcatggca acaagcacaa aatggtctct ctcatattgc 25200
ccttgaggaa attttgcaac taagtaacta ttactgggtc ctagattaca gtctggatta 25260
ttgcgttcct ttcttatttt tattttctcc aattcccttt aataagcatg tactggattc 25320
ataaaaaaac aacataaatg gtaattacaa tattccgcac tggttaaaac ttatgtaaat 25380
aagcattctg ctgctttagc cacaattgca atttatgctc cttctctttc ttaagttccc 25440
agttcccacg tacattcatt cgactgattc aaaagtcatt ttagcttgat agactcttaa 25500
aagttagagt tatcatttct gctatttatt ctttcaatta tccatttgtc cacccatcca 25560
tctgatccat tttgttgatg catgctgtgt ataaaatact acaccagcct ggtgcggtgg 25620
ctcacgcctg taattccagg actttgggag gccaaggcgg gtggatcacc tgaagtcagg 25680
tgtttgagac cagcctggcc aacgtggaaa aaccctgtct ctactaaaaa tacaaaaatt 25740
agccaggcat ggtggcagac gactctaatc ccagctactt aggaggctga accaggagaa 25800
tcgctcgaac ccaggagatg gagtttgcag tgagctgaga tcatgccaat acactccagc 25860
ctgggtgaca gagcaagact ccgtctcaaa aacaaacaaa aaaaatacaa tgccaagcat 25920
cataaaaaat atagtgatat ataagaccta tttgttgtgc tctaggcatt gacatctagc 25980
tgtcaaccat taatatgtgt aggagtctat ctatcaatat tatggactgt gcttgaagac 26040
ttcttcccca atctttttct cttcccatta agtttgaagt gaggttttct gagtgaagta 26100
tcatagtaca tacagtctca ttatttttca aaaatctctg gttatagtac atttctttcc 26160
tttatcccct ttgttcccaa ctatcaaacc attttggata tccagtattg gtatccagta 26220
ttattaaaaa gcaaaacaga gaactattaa caaaaaaatt tgtaggagta attggttgta 26280
tggtatccag tactattaga tagtaaatca gaaaattatt aacaaaaatt ttagacgaat 26340
aatggattgt cttgcccaag tgaattgagt gatttagttg ttctttcatt tttagcaagt 26400
acagctgatc atttgaggcc ttactcattg tttgattttg caaattctta ctattataaa 26460
tgttttgggc tctgagaaag ctgttgtctt aatctgtttg tgctgttata acaaaataca 26520
tgagactggg taatttacaa acaacagaaa tttatttctc atagctctgg aggctgggaa 26580
ctccaagatc aaggcatttg tcttcaggtt cagtatctgg cgagggccgg ttctctactc 26640
ccaagatggt gtcttgtcac tgtatcctcc agagggccaa atgctgtgtt ctcacatggt 26700
agagagatag aaagggccaa ctcactccct caaggccttt cataatgtta ccaattccac 26760
ttgtcagggc tctgcccccg tgactttatt acctctgcaa ggccccacca cttaatacta 26820
tcacgttggt tattacgatt tatcacatga atttcgacca tactagttgc catcctttca 26880
ttttcatata tccttaaaac tttgcctttc tcattttaat gtactttatc cacagtatgc 26940
caacttttcg atacttttgt taacctgtct gacgatatat aggaaactgt aaaagtgcag 27000
tttttgatac actctttagc tgcccgttta cttctactgt cgttagagaa ccccatccat 27060
agtgcatgtg tttattttgt gtatgaacaa agactttata tatagtttgg gtcattttta 27120
ttcattagtg cttcccttat aatctctgaa taccatttta ttagtacata ctgctattct 27180
taatagtaac tagcatgcct gatcatccca aatgtctagg ttcacatttt aaaataagtt 27240
atatctttgg gcttaacagt ttattgaaag gtaacaagga ttgagtcata gttgtatgtt 27300
tttggaagta gaattcaact gtaaatagaa attggttgtt tagatctcac tatatatgaa 27360
aaaatgaagg ctttaggaga aaatctcccc aaagtaccca tttttcatgt gataaatatc 27420
atgaaatgat ttgagaaaaa aatgtatatt tgttacagct aacaaatatt tgtgtttttt 27480
attcttcatg gagagaatga aatttcttct cttctttaca catttctttt tcttattaga 27540
aactaattgg tgcctttata aaaattaact gcagagcact aacgtgtata tataagtatt 27600
atgtagggtg tagggtatgt tcagggtatg gtgtgtgtgt gtgtgtgtgt gtgtgtgtgt 27660
gtgtgtagct gtgtgtgtat ataatgaaat atatggtagt gttgtttcag aaatctgctt 27720
ggtcttccca gagttcattc atcttataaa ttcatctaca ttgatctcta tttttggaat 27780
ccatgaaatg ttttttggca gtacttcctt taatatagtg tgctggaaat ctggaaattt 27840
ctagccagat tagttacaaa aaattagcca gtggttttgc actctctata gaatcaaggc 27900
ccaaggccta ctcttgttac tcagggcctt gttttatctg gcctctttct tttcagccat 27960
atagctctca aatactcaac aaaattcttc attctaggta gacaagtatc ttcaaaatac 28020
ttcccaatta tctaataact gtcttaccac taagaaggct tttatgtctc ctgtctgaat 28080
tttatccatg caaaaaagtc cagcccaagc ctccagaact ccaaaaagtt atccctaact 28140
gctgaaacac agtaatttca ctatgtgaaa tttcactttg gtctcctagc atttgcagat 28200
ataccataca tatccttgat ccttttcctt tcataccttt tatatctaac ccttaagcta 28260
ataattttac ctacactgta attcaaaatg tatccccagt cttaccatgt ctcccttctc 28320
tactgttacc accctaggct aggccttcat catttctcac ctggactcct tccctaacct 28380
ctgaactgat ctgcctgctt ccacttagac acccaaccta gtccattctt gagcagtcgg 28440
aataattctt ttaagaaaga aaccagatca catccccctc tgctcccaac catccagtga 28500
cctcttatca tacatagaat gaaatgcaaa tctttactgt gttttaaagg ccctacatta 28560
tctggacctc agtaacttct tacttcctat cccttttctc cttgtatgcc accctccaac 28620
tacactctaa ctacactgtc tttttccctg ttcttcagac ctgccaacca tattttcact 28680
gctcaattaa tatgtagaaa atgaattgtt tgttaaatgt agactgtttc cttcttaaag 28740
caaagataaa tgacattgtc ttcaaaaaca actaactgcc cagaattcct gattttaatt 28800
ttaaaaagac aaactgcaag aatgtgttaa acagtaagga aacaattcac tacttcagaa 28860
ttctatatga tttcactgca cgttagtaat tttgtatatt atagaatatg agggtattct 28920
aataaactta actctatgct gtatacttat catgatagct cattttctta tatgtttata 28980
acagcactac ttattgtaca tggatacgtg ggaaataaat taattttctc cttaagaaca 29040
aagcaaccat ttcactcatg agataaatct tgaagattta aaaactactt ataattaatt 29100
atacattatt catataatgt taagtatttt cttagtaaac cacataattt agaatggcaa 29160
ttggacagat gggcagaacc acatgcatcc actattaggc agttggtgag cataagatgc 29220
cagaaagaag attaggaata tcaaggcagg gagcttccga tcgctcttga aaacattgac 29280
ccttcactcc tcactctcca cgatgcattt cctttgaaaa gtaatgcctt ccaaaacaaa 29340
gttctctgtt ttatatctaa acttactcaa tagtttctca tggttattga tatataaaaa 29400
ataaagtaaa atgtttaggc agaccaaaag aagaatttcc ccctccctct gccttttatg 29460
ccaaggtgac agctatgaaa tgtacagtac gtttcctctg caaggaatgt agcagtgttc 29520
cattgcaaga agatgagagg gagagaaagg ttgcacgctg aggaatatag tgtcatttgt 29580
cactgcctag actcatcagc tgtgtggaac tctgagaggc accaggcttc tttatttatt 29640
tcttcagaaa cttcagcaaa aaagatttca ttaggagcag agaaaaatgt gaaaaacgaa 29700
ttagcttttg tgatggggag tagtcatctc tgaatattga tcaagattaa gagggttgtc 29760
ttcgtaactt cttttatcca tagtctatac tgatttaact agaaaactaa tttcaggtgg 29820
tatttcgggt gtggcagatc tttatagtaa atgaagaatc tagtcaaatc tactgaaaaa 29880
ctctgcttac tttaatgttt gatctggttg aaaccatttt agcttaacaa tccttcctct 29940
gaaacaggga atcaattgat atcctacagc aaaattatgt ggaagggcca ttagcttcac 30000
atccaatgca aattttgcct gtgtttactc ttccccaatc caaaatatat cagatcctag 30060
atgccagtga aatcgtttga gctagatggc ttgagggtca tagctttttt catttcctgt 30120
tctcagacct cttataattg atagaataaa atcagaagag ccctagagct gtcccaccta 30180
ttctgcctca caaaagtaga agtaatggca accactatca tagggatcat gctcaccttt 30240
ttcttaccag acaaatttgg atattagctt gaaattaata ccttccttaa aatgttggaa 30300
tttggttata tgcgaaattt tgctctattt attcattata ttttgtatgg aattattttt 30360
gccctatatt ttcacttaag tgttctctac ccaagatttt aattgaaccc aaatcagcca 30420
gacacacaga catggatttt gctgccacca aggttaattc ttcttttaaa gttaactttt 30480
aaaatttggt aaaatatagc tttgaaaatt tgcattcgtc tagtgtttgt tatgtatttc 30540
ccccttttgt ttgattatat gtctatattt ttcttgtaga aattgatttt taacctgctt 30600
tttatgttag cttttatgag cttctgtctg aattctgaat atgtctttct taatgtcttc 30660
taaatgtttc tttctggatt attaaaagat ttattaggct tttaataatt atatttgtta 30720
ccttagggaa tgtgtttgaa aatattttaa atggaattgc cagttaacac agcattgaac 30780
tttttcttgt tagagataca ttgttttcta ggcattttat tgggagagaa gttagtatga 30840
tataatgtct ttggctgata ttaactcttc taagatgcat tgtttctgag aacaccattg 30900
tctgatttca ttcagggaaa tttcacacaa gccagtagag tcaatacttt tttcaagacc 30960
tgttaattga tatatataaa aacttgccat tgtttacatg cccatttcag atcctttatg 31020
tgacctaagc tagaaatgca ttttaacagc atttgttttt ccaaaaatat ttatttattt 31080
atttattata gagatagcgt ctctctatgt tgcccaggct ggcctcgaac tcctgggctc 31140
aagcaattct cctgcctcgg cctcccaaca gtgctgggat acaggtgtga gccattgtgc 31200
caggcccttg tttttatttt ttttgaacat tgtattttga aaggggtttg aaggtgatcc 31260
ctagatagca accagtaatg attcgagcag caaaacaatc taaaaagtaa ttttataaga 31320
aaatgcagaa cataaatgag cccataaaaa attatattag gttctattta cattactacc 31380
ttctttcaca tgtaatattt cactaacatt taatgaattt ctgtgcagtg ccatatacca 31440
ttatgaattc taggatagaa gaatgagtga gaaatgttct taggccttag gaagaaggaa 31500
caagcatctc tgtgtaatag ttatttcaac tcttctttta cacctcattc ccatattaaa 31560
tctcagaaaa gctaaagtaa tagctatccc agatctattt tagactccag acacttactt 31620
caatgtcttg ttctccttat cagactggaa tcattccaaa cctcttaact tctgggcaac 31680
catgataatg cgacagaaag gacactaaat ctgtcgcaaa tttatcttga tattctatcc 31740
agtcttactt ggtactgaag gtcacaagta aaataaggtg gttgtttttt gtttgttttt 31800
ttttttttga cagaagagaa aagaacactg tgagcacaga gtgaatgtct aacattgatt 31860
cttgagtagc aggaattctc tatgcgagag gatctctatg caaaaagatc tcatattcta 31920
gcacaattta aggatctcta tgcaaagata tcccatattt tagcattatc aataagctat 31980
ggggtaatat attgtatgtg gtgtggcttg aattctagaa atttgatttc tagaaatggt 32040
ccctgtagtt aaggatatat aatgtggccg tctccagttt tctatgagga ataggaaaat 32100
actatcatta ttagctgtgt gaccatggac aacttgcttc gttcttcagt tgcatcatct 32160
gtataaaata agaataagaa aatttacatc tgcaaggtgt gatggagatc acatgggata 32220
attgtggtcc cagagcctgg cacaaaaggg cttaatattt ataatcctcc ccatttctcc 32280
gtatactcta aaggaagttt attgcttatc aaattgtgcc gtggttagtt gtacagcttc 32340
cctgccaaat tgtaaactcc aacactaatg tgacgttaca ttttatatag tgctatgatt 32400
ttcaaattgt ttgcataatt tcaaatacac agtaaattgc tttttattag tataattatt 32460
gctattgtca atattattat tacaacagct tcacagtaag atgggcagaa aaaaatttaa 32520
tttccatttt acaaatgcac ttttgaggct cacagaagtc aaatagacca aagtcacagg 32580
gctagtgagg gacccagaag aaacaaattg taattcactg attccaagtt cagtggttgc 32640
cttactgcat cataaaggct attacacaat ccaggtgtat catatgattc ttgtctatat 32700
attcatacat atcagaaaaa gtgttctact caaaattgct agcaatcaac agatactgat 32760
agtcattagt acttaaatct ttatcaaatg aaatattaat acccatgaaa gagaggacaa 32820
tgaaaggttt gtatcatttg tatgtcacaa gtcaactttt ttcaatcact cattattagt 32880
ttaactgtaa aaaattattt acatttagcg tgaaactttc ctgtattctc aacatatttc 32940
cttcggtaga aaagcaaacc tccagttctc tgttctttgc ttggatactt gccagtttgt 33000
aactcagcta tcaaacagta aagctcacaa aacacttatt aaaatgacta aaatccaaaa 33060
caccaagagc acagcatgct ggtgagatgt ggagcaacaa gaactttcat tcattcacta 33120
atgctggcaa tacaaaatgg tacagtaact ttggaagata ggttgacaat ttcttacgaa 33180
gctaaactat acttaacata tatatttgtc cattttcaca gtgctaaaaa gaagttcccg 33240
agactgggaa atttataaag gaaagaggtt tatttaattg actcacagct cagcatggct 33300
gaggaggcct cagaaagctt ataatcatgg tggaaggaga aggggaagca aggcacctac 33360
ttcacaaggt gacaggaagg agaatgaatg caggaggaac taccaaacac ataaaaccat 33420
tagctctcgt gagaactcac tcgctatcat gagaacagca tgggggaaac agctctcatg 33480
atctagttac ctccacctgg tctctccctt gacatgtggg gattatgggg attataattc 33540
aagatgagat ttgggtgggg acacaaagcc taaccatatc accatatgat ccaaaatcat 33600
gctacatgat attcacccaa aggaaatgta aactgtgtcc acaccaaaac ctgcacatgc 33660
acgtttatag cagctttatt cataattgcc aaaacttgga agcaaccaag atgttcctca 33720
ataggtgaat gaacaaaaag actggcacat gtactcaatg gaatattatt cagtgataaa 33780
aagaaatgag ctatcaagcc acaaaaacac atggagaaaa cttaggtacg taagccagtt 33840
tgaaaggttg cattctatat gattccaata tatgacattc tgaaagagac aaaattctgg 33900
agacagtaaa aagatcagtg attgcctggg gctctgagaa agtgcagagg gatgaatggg 33960
tgaagcacat ggcatgttta ggacagtgaa actattctct atgatactgt catggtggat 34020
acatgacctt atacctttgt taaaactcag aattttacaa tacagagtga attctaatat 34080
aaactatgga ctttagttgt aataaggtat caatgttatt tcataagttt taataatgta 34140
ccacactaat gcaaaattat aataataggg gaattggggg aagggtaatg gagtatatgg 34200
gaatgcactg taatctcagt acaattattc cacaaaccta aaacttcttt caaaaataca 34260
agctattggt caggtgtgat ggcttatacc agtaatctca gcactttggg aagtcaagac 34320
cctcagatca cttgaggcca ggagttcgag accagcctgg ccaacatggt gaaatcctgt 34380
ctctactaaa aatacaaaaa aaaaaaaaga aagaaagaaa agaaagaaag aacagaagaa 34440
ataaaagaaa gaaaggaaag aaagaaagaa gaaaagaaag aaagagaaag agagaaagaa 34500
agaaggaaag aaagaaacag aaagagagaa agaaagaaag aaaaagaaag aaagaaagaa 34560
agaaagaaaa gaaagacaga tgcggttgct catgcttgta atcacaacta ctcgggagac 34620
tgaggcatga gaatcgcctg aactcagaag gtggaggttg cagtagggtg agattacgcc 34680
actgcactcc agcctgggtg acagagcaag gctctgtctc aaaaaaaaaa aaaaaaagct 34740
attaaaaata tgtaaagctc agtctagata cagtaccaga atagtaggaa ctttatttca 34800
cctgtcctac aaattatggt tgtgtgccac ttgggtaaaa ctcagaatcc aaatatgtga 34860
atgtaagatt tatggggaaa ttatttgtat ttcaaaataa tccttaatga atgcactcct 34920
tctaaagtag ccattaataa agcagttaat gtttcattta attatagatt aatgtacata 34980
agatatgcca ggaatgcaat taggaactgg gaagggggtg ttattctaat aacttccaca 35040
tagcattgtg agacattttc tgctttcttc aaatttcatt taattacatt ttaaacaaat 35100
atttttgtga gcctattata tagtccttcg ctagcactga ggagacatgc tttgtgacct 35160
tggtgatttc acattcaaat ttccctttca cctacactct tccttgtttt ttcatgcctg 35220
tgtagattgt aaattcttcc tcagattaag acattttatt cacctttgta acatccacag 35280
tatctagcac aatcagtgcc ttcaaaaaca attggcctca agaattgatt gactcaatga 35340
gtgactgaaa gactaaatta ataagtacac atctatttgt acttccctgc ttacttataa 35400
ggtatgacaa tgaaatactg agacagttat acattactta cggactcaat ctcatttctt 35460
tacaatctct attcttcttt tttgagtata atgttatttt acaattccac taacttgtca 35520
ctctttatta taaattcata tctccatttc acctgagaat aataaaggca aggaagtatt 35580
ttaaatgatc ttgtttttta taactagcat tcattgagca aatcaaagta tgaaaataat 35640
ataggtgtca gtgattatta taaagttgta tgcacaaaac attccaatga ttggggccaa 35700
tacagagaaa acatctcaat atttggaatt ttgcttttct gtaaatactt tgatatgtac 35760
ttacatcata tcaattataa ctcctgctga aaacaaacag tgcacacaaa tttggtagtt 35820
ggaggagact ttataaaggg actaattacg aaggtttaga ccgggttagg aaaaacacac 35880
ggaatagtgc aatactttag gatggcaaca gcgagcaccg ttataaccac taggccaaaa 35940
tgaactaaat gaacagggag attaccattt atcagaaaaa gagggagaaa ggaaggagag 36000
atgaccaagc aagtcctatg tgaagacggc tgcctgactt gagctgtgtg atctttggac 36060
tgataccacc tgcctgcact ggcctagcag ggcgagaata gtcaatatct ggaaaatgga 36120
tcacctgacc ttactttcct ccctccctgt ttcctctttg tggtgtttcc actggccaaa 36180
ctcacagcgt agacaaaagg agtgcattga tgtagcagtg gttctaatcc agggccaatt 36240
gtgctcccag ggaacattag tggttatcac agctcagggg aggaagggag aggagtggag 36300
tgctactatg attcactgag ggattttttt aaacatctac aatgcacagg acatccttcc 36360
acaacaaagt atccagttaa aaaatgtcat tactgccaag gttgaaaaac cgtggtgtag 36420
tcagtacaat tcatcttctc caggcacagt gcaggagtgg ggtggagtgt ctgaagggga 36480
agaaggaaga aaccagcaca ccccacaaaa gtaaccaatg caaataccaa ataggaaaag 36540
acagcactta aaatacaaaa gtctcaggaa tatatctgat agtgttttat ggaatttatt 36600
aaaatttagc ctggagtgag taatatttag caagccaggt ttgtctttag agaaatcctt 36660
gtggggttta tacaaggatt tattaacaaa gggcacacac aatactcata ttacagtcag 36720
tctggttatg taaaacatgg gcaagaatgt aataggacaa tgtgatgtat tcacaaagga 36780
ttttaggact acacagataa tcctctaatg ctttcactta cgtactatga aaggctatag 36840
tttgcatagt gatatagcca cgtaagatag taaacttgac attcatgcag ctatacatgt 36900
ttgcacacac caggatgcat gccctttcta cctggttgat tttttattct tttattaatc 36960
tctaatttat tccccagaac actctccata aaaactttct cacaacttaa atctttaatc 37020
tattgtgtgg atttctgact cattctccaa gcttttcctc ttccctccgc aatgccttat 37080
agtcttatga ctatttatcc ctttgcctac atttctagcc agatctcttg cctgatacac 37140
actctcatat ttctctttgc acgctacaca tttttattta gatatcacac tactactttg 37200
atttcaacag gtctcagttt aacttaattt ttccttcaag caaggagtcc cttcatatca 37260
gttatcacca ttggcaccag aatttttctt atgacttccc atgacctaca atataaacca 37320
tataaatcac tgatgcctcc atagttccct ccctctcaaa tttagccata agatgatttt 37380
aggatccttg ttttttccaa tctctctttc attctctccc ccatctcttc cattatgaag 37440
gtttggatag gacacaactc atgcctagat tagtgcaata gatgctgagc ctgtgcagcg 37500
gtagtttagc tttctctcct ggttaacttt aactgccaca tatatcactt cacacgtcat 37560
ttttcattca aacgtattta actggctctt cattcataag aagctggaat ttgtcgtttg 37620
actgatattt taaagatttt atattttttc tccatcctcg ttctaatgtt gtatcttgtg 37680
tcatttgttc attcataaac ttaagactta gctaaccact gagcatccag gaaattcagt 37740
atctatcatg tgaattctct aatactggtt gatccattgt caccagagca tagcaggctt 37800
ctcctgcctt tatgtatgtt tgtcatatag ttcatgccta aaattctttc ttaaatctta 37860
aattcctaag atacacactt ttgcccaaga tcacagtaat ctctgccata atctctgctg 37920
gaatctgttc actgtgttgc tcctgctaaa cttcttacag atgacttttt ttctttttgg 37980
tttccctggt atctagtata atttcttata taggtactca ataaatgttt cctgttgatc 38040
tctacaccta ctctgtacaa taccatagtg actagacaca tgttgctatc aagcatttca 38100
aaagtagcta gcctgagttg agatataggg gtaaaataca caacagattt caagacatat 38160
tatgaaaaaa acccataaaa tttctcagta atttttttat agattacatg tagaaactat 38220
aacattttga ataagttgta tcaaataaaa tataaaattc acccggttct ttttaatttg 38280
ttaaatgtgg tggctagaaa atttaaaatt acataattgg ctcacagaat aattataatg 38340
gatggtattg ctttagatca agtttgtcta acccgtggcc catgggccac aagcggccca 38400
ggatggtttt gaatgagatc caacacaaat gtgtgaactt ccttaaaaca ttatgaattt 38460
tttgtttgtt ttgtttttgt ttttttctca tcagctatca tgagtgttag tgtattttat 38520
gcatggctca agacaattaa ttcttcttca aatatggccc agggaagcca aaagactgga 38580
caaccctgct ttagatagta aagcatatga gtagttaatg tgtactataa gcagtgtgat 38640
ctgatagact atttaatgtt gtttgatggt acattattca agtcgattat tatgtctacc 38700
tatgcagttt aacgacggta atgagagagg gcagcttgat tacaggtctt atcttttgac 38760
taacttgcta ggccacctga gaaggaccca aattatctga atgcttaact caactaattt 38820
gtattcactt gaagaatttc aaggatgttt atatgccatc aacttgcttt aaattttttc 38880
tctcagtgaa aatttttctt aaaatgagta tgtggtattc aaatttatcc ttgttttcta 38940
tgattatctt ttcatagcac tgtggtttcc aggaaccttt ttttttttga gatgcattct 39000
acatgtaact attgcacagt ttgcatgtag taaggttcat tattcttcta cttttccaaa 39060
cacctggcat gtttacttga ggttggtaca ccttgtatcc cagattttgc tgtttttaac 39120
ttaaatattg aatattttga ttaaacatta tggaaagttt aaatgggtca agaaaaatag 39180
cttttcttcc catgaagaac aatacggcat aggagttaag agcatagatt taaagtcaga 39240
aaacctgtgc tgcctacttg tgcaaagtca cttacatgct gtacttctgt ttcttcatct 39300
gtaagttcta cccctaggta tttacttaag attaatggaa gcatatgttc atacaatgac 39360
ttgtacagaa ttattcacga tagcattact cttaatagct ctaactggta acaacacaat 39420
aatcaatcaa caattgtgct gtattcatac agcagaatac tacttagcaa caaaaatgga 39480
atggactact gataacctca acaacatgga tgaatctcaa aactatcatg ctgtgtgatg 39540
ccaggcacaa atcagtacat actataattc cagaaaagac aaatgtcatc catggtaaca 39600
acaagatcca tgcttgctgg aggtagaggc atcagttcag tcattcagga agctgattcc 39660
aagatggtgt tagaattaca accatccaca agagatttat tgcaggcaat agctatgaaa 39720
ggtagaaaga gaacaggaga aaaaccaggc aaggaaaaac cacaatgtag ttgtgatatc 39780
acttcaaagg gaggcagaag gaaggagaat tgggtaggaa tagccacaga ttacagtgca 39840
gttacaagaa agtcttggct tccaacaaag gttacttgtt gaggagtcat gcattaggca 39900
gacatgtctg ggctgtagtt tccttgctgc tcccagtcat tggctggagg ccagtctggg 39960
ttcctgtgct gtggtggatc ccattgctgc tgcagcagga ggccaatagc actcctggca 40020
gctaattgga gagaaaagat ccaagaggtg taccttcatg gctaccccca tggggctggg 40080
gtggaggtgg aggagaagga gaaggaatta actagaaaaa ggcacaaagg aaaattgggg 40140
aaaataatga agatatatga tttctcaatt gtggtggtcg ttacatgggt ttattaatgc 40200
atcaaaactc aagaaatgta catttaaaat gagtgcatat gattgtaagt gaattatacc 40260
tcaatatagt taatttttta aaaatcatag atttctttat atttaatgca tgaacataaa 40320
cctaagacac tcctccactc caaaacttaa ttaccttgtg atcagcagag cagaaggtac 40380
tttgtgatat ataggtagag aagatgaagt cttgtgacat ttaacaaggg acaggaaaat 40440
ggaccttgtc ctaagttacc aaactgcaaa aatatcacct acaaaggcta ttcataacat 40500
acattttcaa gggggttaca atatttgcct actataaaat tttggatctg taaaggggtt 40560
aaattatttg tgcaggggaa taaacatcaa agaaacatta agaggtccag agaagtaaaa 40620
taggaagggt cttttggcta gaggagatat ttaactttca gaacatgtgg aattaagttg 40680
tattgattat gatctgatct tcttccccct aaatttgatc ctcttcctgt aatctattgt 40740
ttccatcatc ttcaactctt ccctttccct ctcccttgtc cctcagttct agtcaatcac 40800
aaagtcctac agtttcactt tctgtatacc ttatttctgg aattcatctc tagacttcaa 40860
aatatatata tatatatttt tttttttgag atggagtctc gctctgttgc ccaggctgga 40920
gtgccgtggt gcaatctcag ctcacagcag cctctgccac ccaggttcaa gcgattctcc 40980
tagttcagcc tcctgagtag ctgggattac aggcatctgc caccacgcct ggttaatttt 41040
tgtattttca gtagagatgg ggtttcgcca tgttggccag gctgatctcg aactcctgac 41100
ctcaggtgat ccacccgcgt cagcctccca aagtgctgga attacaggtg tgagccactg 41160
cttccagccc aaaatatctt aagtagataa ttgcacgact aatctctgct tttctctccc 41220
agcagccttc caaattcatg tctcacagct gacagagttg ttcctgcctt cagattcatg 41280
acctggctct gtgttctagc tcaggctttc tctctcatat cacctcttgc ctctctgttg 41340
cccccatatt ttcccctctg gttggttggt gctcctttgg aaccctctgc atatcttttc 41400
aagaatatta tgacttatta tgcctataaa ctttgtttaa ttatttattt ctaaaatttg 41460
acagggaact ttccgaaggc aggtattgtg tctttctcat ttaaaagcaa attctcgcct 41520
ggcatggtgg ctcatgcctg taatcccaca ctttgggagg ctaaggtgga cagatcactt 41580
gagcctagga gttcatgacc agcctgggca acacagttag accaaaaaaa aaatatatac 41640
gaaaattagc ctggcatggt ggcacacccc cgtagtctca gctagtctgg tagctgaggt 41700
gagaggatca cttgagcctg gatggttgag gttgcagtga gctgtgattg tatcactgca 41760
ctccagcctg ggcaaaaaag taagatcctg tctcaaaaaa aaaaaaaaaa aaaattagtg 41820
aatcctcagt gtttaaaaag tccataaaca tactaaacat agaagacctc caaatgaaat 41880
taatcaatta ttatttagtg ggttgcttct cttttgtttt aatatagttt taacaaagag 41940
taaaagttat gatcttttta tatgtaaaat aaataatgcc gggtttgaca taaattttag 42000
gaaaactaga gacgctactt cctaaaaatt ttctttctat aatcttccta aatatttttc 42060
cataaagtac aaaataatag aaaaaaatta agagattgag tatcctttca ggaagtgata 42120
tgacaaatag ggttcgagaa ctatttgaat tctcaccact tttcataagg gcagatctca 42180
agttaaattt ttctattcga atttaaatga ctttcactgg aataccatta cagaaaagct 42240
tctgtgttta gatggcaata tggagtttct tttcttggaa tattaattga aggagaagtc 42300
ttaatttttt aagtctatat ctccgtatat atttgaacct attttatatg ttagtccttc 42360
tctttagtaa ccttcatcca cagtgaacaa gatttaccct tacctttaag cagtagcggc 42420
tactttatgt gaagtgaaca gctgcttttt ttatctgcat ctagacatca agtagtccag 42480
agtcctttct aacaccctag caatagaagt aagaatattt tgaccattcc atgacttgat 42540
gatacttcta gtaataatac tgtattatta aaaacaaaca aacctttgtg cagtggtaat 42600
tgaagcagtt ccttgggaac atgtattaag tactttttag cagttaagtc cactctctgt 42660
aggttaagga atatttaaat aaaataatgt ggcaaatgag ttcaagatga taaatgcgat 42720
gagaactaaa acagctttaa ttttatgtgg gaaataaata gaggaaaagt acattacagg 42780
gctcctggac ttatttcttt cttcaaagtg tttctcctag cgaatattat tactattttt 42840
tctcttaagt aaaaaataca caaagtatga atctacacag gataataata ttgaagttaa 42900
ggatgatgtc tcctccttca ctctccaaaa tactatttac ttggcttcat ggaaatctct 42960
ctcactccaa ttccaccgtg tcaactgagg tcttctgttc tttctctccc tatagcatat 43020
tcctgttaca taaatcctaa actgtgtcgt gttagtcaca cactgtaacc tctagataag 43080
cgcctgtcca gaggttctca atcagagcct tgcaaatatg tattaaatca atgggtcatc 43140
ttcagtgtct cagtgggccc ttggatatgt tttgcagact gctgtgagta tgtagggatg 43200
tccagtatcg agggaagtgt ggatggcttt cattggttct tatagggctg aagaacacat 43260
agagcagtaa gcacttctac tgtagggaga gatcgagctt ctcccatccc cactgctggc 43320
accaccacca ccctacaccc cattttgagt tctgaaagtg aatccttgag aaagaacaca 43380
caaaacaacc atcataatag tgggcacagc tgtgggtggt agaataacat tcccaagctt 43440
cttttcctac acatgattaa tattaattca gcaaacattt attcagctcc tacttttaaa 43500
caggcactat tctaggtact aaagacatag aggcaaagca tacaagactc tgcctttgtg 43560
aaacaattaa gaaataagta aaaagaaaag aaacagaaaa ggcaatttgg atagtgtcag 43620
gtgctataaa gaaaacaaaa tgccatttta ataaataata ataatacaat gttttcatac 43680
tatgtgctag acactatgct agtaggtatt tatagacata acctcaatta atcctcaaaa 43740
tggcatgttg atatcaatac cccaagttta catatgagac ttaagatgtc tgagtatatt 43800
cccccaggta acaattaata tgcacaataa aactttttgc tcattcattt attaacctat 43860
gttgattgag tacctatttt gtgtcaggca tcattttaag gcacctggat atagttatga 43920
acaaacaaat aaaaatctct gccctcaaat aattaatatc tcacagaggt taggcaaaat 43980
ataatcagaa aataagtata acgtatagga tgccagatca tgaaagaagc tatgaatggc 44040
atcaagaagc tggaaaaggc aaggagacag attttctcct agagtctcca aaacagaaca 44100
cagtcctgcc gacaccttaa ctttaggcta gtgagacccc tattggactt cagacttaca 44160
atcccacaat gtaataaatt tgtggtaatt cagtagggga acaatagaaa actaatacga 44220
tatcaaaaca aattatatca tagaacaaga aaatgtaatt gtgacaaata atacctacaa 44280
aaatgttgta aatgctaggc aaataatgtg tttaaagcac ttaggccaat gttcaacgta 44340
aagtaattca tgctataata tcatcatcat cattaccaat atttaggggc tctaacaaat 44400
gatgtacgtg taagcagatg taagaaaatt tccttgctga agaggaggta ttaatagagt 44460
atataacaat agataacaaa ttccaaataa aggcaaacta aatgttttat tggattaaat 44520
ttaattttaa aaactacaag aggccgggcg cggtggctca cgcctataat cccagcactt 44580
tggaaggctg aggtgggtgg atcacgaggt caggagatcg agaccatcct ggccaacatg 44640
gtgaaacgct gtctctacta aaaatacaaa aattagctgg gcctggtggc gcgtgcctgt 44700
aatctcagct atttgggagg ctgaggcaag agaatcactt gaacaaccaa ggagtcggag 44760
gttgcagtga gccaagattg tgccactgca ctccagcctg gcaacagagt gagatcccgt 44820
ctcaacaaca acaacaacaa caacaacaac aacaacaaca acaacaacaa aactgtgaga 44880
tccatggtgg gcttttaaga ggaaaatgca agctaaggtt tgtttagact ctgagtactg 44940
catgtgtaaa aataaaggca tgatgaaaag atcaagagat tagagtgata ctttttatct 45000
actagtgtca gagtcatgac caggggattg gctatgagaa tacataagct gtgccaggag 45060
taatccaagg agattgtttc aatttggaag agtgtccaca gaatgattct catactagac 45120
gttgggctat tgtaaagaaa gttggtaggt actccatcgc taggatcata tcagggagaa 45180
attgaacagg atggccctaa tgaccctgtt gtacccctag cttatggatt aggcaagtca 45240
cttctactcg tataccctgt ttccccattt gtaaataaga ggatgtgtta ctctaaggat 45300
ctctaagatt ctttgcagtt gttaaattgc atagctctcc actgattcca tggtggaaat 45360
ttgctattct attacaaata ttctaaatgt atgagatatc agacatactc atttaaaaaa 45420
caaaatacaa aaaataagta ttctacaaat aaacacagat aatgtttaaa ttctatatgt 45480
ctttgtttct cttcagaagc atccaaaata caaaccatct aagaggcaag aaaatgtcgt 45540
gatgttccta gtgcaagtta aaaagatttg ctttcctcaa gtcggaaagc ccttctcatt 45600
tttgaggttt ttttcttctt ttttttttca agtgaaagca ttttggagga gtcaatatcc 45660
atctttaaag gtagccaggt cacatgtata catatgtaac taacctgcac aatgtgcaca 45720
tgtaccctaa aacttaaagt ataatttaaa aaaaaagaat ttaaataaaa aaagaaaatc 45780
agagagaaaa aaaaaaagat gcatgtgcac cctgatacta ccatccatag tgatacggtt 45840
tggctttgtg tccccaccca aatctcatct tgaattgtaa cccccatgtg ttgagggagg 45900
gaccttatgg gaggtgattg gatcatgggg gtagtttctc catgctgttc tcatgatagt 45960
gaatgagttc tcataagatc taatggttta aaatcatggc acttcctttt gctctctctt 46020
tctcctgcca tgtgaggtgt gccttgcttc cccttcccct tctgctatga ttgtaagttt 46080
cctgaggcct cctcagctat gcagaacggt gagtcaatta aacttctttc tttataaaaa 46140
aaaaaaaaaa aaaaaaggta gccaggtaaa aattacttgt ttccaggaca ttttcacctg 46200
aaagaagcat tgtcatataa catagaagca agaaatccag tagtgggggt tatttaaaaa 46260
tagctggaaa atttcaatca gcatgagttt gaagcaacaa tttatcatca ccttttatgg 46320
tgggtggggt taagaacatt tcagcgggca aagtggtggt gatggggaag agacaccagg 46380
ggaggtgatt cccattgcat tgctttgtaa acagaggcac aggttcttca tttttgtcac 46440
acaaaatcac agctatgcag aatttattaa tttattcttc tgagacaaga aaaaagccac 46500
caaaggaaac caacagcttg ctcctctcac actgggggaa ccatatgaga gacttatcta 46560
tccctgactt taattttgac ctgaggagag ctcctcttaa ggaaaacaaa ttaattcaat 46620
gactatacta cttaatcatt gacctttatt taataagaga tttttccata ggatatgctg 46680
agctgtctca cttacatcag ttgtgtctcc tgaggtgggt gacaggagac cacaaatatt 46740
gcatagcaca caaatcgtta atagcagctg tataccaaac cattacctaa atatgtagag 46800
tacaattcat tctcactaat gtcagagagc atgctataaa atggtgaatc cggacagctg 46860
aagatactga ataataacct ctattttgaa caagtttaca gtgttccaat cagtaattaa 46920
attgatacct gatgaatata tgtgtgtgta tgtattcata gcagagatgg ttttcctgag 46980
ataaggattt tgttattcgg ataggctgct gctggaattg tccttctacc cttgtttctt 47040
tgtccttagt catcactcat acctctttcc actcttctgc catcactttt gtcaccaaag 47100
tcatggtcct ttccccgccg attgctgctg caggtctagg gcaccaagac ttaggcagca 47160
ctcaccatgt gccaagaact ggaccacagg taccatccag cattgctcat ggagactctg 47220
tccctttctg taggacaccc tccttttagc tagcaacccc tccaccacct agagcctctg 47280
gacctctcat tttaatatta agaactagga aaacttaccg ctgagaataa ctagtacaac 47340
tagaactggt agagaaatct gggtctcttg ggaatggatt tttaggcttt attgattaga 47400
ggtgtattaa taatgcagtg ttatagtttc atgacataac gaataaaaaa gttcattttg 47460
gacttgcctt tcagctccct aggagctaaa agacgtattt aatgtaactt gtgtggtgga 47520
aataagttct tttttcaggc aaaagatgtg caaacccatc tggggaagaa acattaaaaa 47580
ctaaggagac agtgtcctag ataactatgt tcttttcctg ttttagtcta aaataatgat 47640
tagttttctt atatatcttc atttgtcttg gttcctttta gcccaattta ataatattat 47700
tgcagatatt gatgaaaacc tttaccttcc tcttaattca tcaaagtact tgataaaatt 47760
tatacatagt acattaattg ggaggttttt atgagattaa ttaatataat gaactgatgt 47820
tgaaattatt taaaacctga attattattg tattaagtag gacacttaat acagttaatc 47880
agttctgtct ttattcattt gtgagaattt ttggcaagct attgtgaata ttcagggaag 47940
ggaatgtatt tttagcagga atcttatacc tcctacatag aaatgaagca tttactgaaa 48000
catccatgaa acaaaatgtt tctgaatgtg tactatacac ttgttataag ccccttttct 48060
tctgtagcta tattttggag aaaaatcttt gctttgacaa aaaaaattat gttgacttac 48120
acatatattt tataactaag cagtgtttgg tttgtgataa aggatacaaa aatataaaaa 48180
tgttcagcac acgtaagtaa ggccttgttg acagtgtgag ttatgctact ggatactcaa 48240
aaggaacatt cagtgttctc aggtggtctc tagactgtct caagcctagg aagatatttt 48300
ataagcaaag gaataagaga aggaagattc agatttaatc caagtgaaga attcagtttt 48360
gtgtgcctta tcctgttatt ttgagaggca gccaaaagat gctggtcagc aaggagaatt 48420
gtaagttggg cagccaactc tgatttctca acctcttagc tgttttctta aactcagaat 48480
ttttaatgaa tttaaatgtc catatcaggt agactttggg gatgctttta ccagtgattt 48540
tcagaatgtt actttctggc atttcttttc acgtagcatt atattaaaaa tgaattcatt 48600
catccacctt cccttgtcct tactaatttt ccctcctact cccttccccc ttgttcttgc 48660
catggggaca tgcaaacact ggtggttgat gtctgagcaa ggctgctgac agggggagga 48720
aggagatgtc aagcagaggt caatggcagt gtgcccagca gcctaggaag taggagggaa 48780
aagagagaga gacagagatg gtggatgaaa gagaaagcca ggatgattat ggtggttatg 48840
atacttgtca tgctgaacac ccaattgagc acccaataag cacataataa tttaatcatc 48900
ctctggcttg gatggcagtg ttctatcagt gttgacttcc tggttgtgac agttttacag 48960
tgttagtgta gaagagaatc cttgctttag agaggtactt actgaagtac ttagggttaa 49020
tgcaccattg tgctggaaaa agatacgcac acacacgcac acacacacac acacacactc 49080
tcacacacac gcacaaatac atccatgtgt taggcagagg gagcaaatga ggtaaaatgt 49140
taacaattag gaattctggg tgaagtggat agagggactc tttgactgtt cttgaaactt 49200
ctctatacat ttgatctgtt tcaaattctt cagaaaatca aactacaaaa acttaattca 49260
tttagtgaac atctactgaa catctgtata ttaaatagtg ttaaatgaat gtcaattaaa 49320
atgctcaaac acagtagagg ttgattctca ttcacataag tccatggtag gtgtttttgg 49380
caggtgggtg agtttctccc ttagggagat tgaggaaccc agactcctcc caagttgcag 49440
ccccaccgtc ttctgagggg atgcatccat acccacttcg aagtagcata cattatttcc 49500
tttctcattc ctttggatac cagccacaat ttattcaagg tagacagaaa attgtagtat 49560
atagccatat gccctgacaa agaagggaga acagattttg gtggacaact agcaaactct 49620
gatacaatct gttattaagc actgtgtgtg gatagatgct aactagaagg agattatctt 49680
cccttcagca aatataaact gaatgccgtt tatttggttg aaactaagct agatcatggg 49740
agtatagaaa ttttataaga agacatagtc acttctgtca gtgagctcaa gaagaattag 49800
tatgcggaat gtaatcatac ctacaggggg cttgtgccac ttaagtaaaa tgaaacatta 49860
ttttgagtac aatttagcaa taaatgtact acgagatcat taaaaatcat gtttgaatgt 49920
tattgtgtca aggatgggaa aaagactttt gggttgtaga cttgataatt atagttaaaa 49980
acagttttta ttcttgttta gtcttatttt ttatgtttaa acatatttat acttgctaac 50040
atttatactt gctaagtaaa gactgttttt acaaccatga caagaacaaa acatattagt 50100
aatgcaaatg ccacatttcc tacaatcaac taatcacact aacatatttg catggaagaa 50160
tcactgggat tgatctggcc acgtgtgtag tcatgcccaa aatgtgaagt ccatctgttt 50220
tgcaattttt tttaaccact gttatccaaa tgctccttgg atttttttta ttagtggata 50280
tattttggag gtcagacacc ctcttggcta gatcatcacc tttataacaa atatatatac 50340
tattctcatg gaaatatatt tagacattgc cctactggga atttttttca agtaattaat 50400
gtacagcttg tgcaacagct tgatcttggc ttcatggaaa taattcactc ttagcagcat 50460
ctaatgccac aaagcattta tggatgtcag ctcagaactt acttttattt atctctgagt 50520
tacttttttt tttttttttt tgagacagag tctcactctg tctttggctt gtccctaacc 50580
tcttaacaga cttaatatta agctccattt cactcagtcg ttctgttgtc atataaatga 50640
gacattctac aagcatagtt tttagtttct gccagagcat catacaacat tgtgagctat 50700
gatgaagata aagacctaga gaagatattt aatatgaagt tcattatcta atatttggta 50760
tgtgtggcaa aatagcaatc tactgcttgg ttctgctgta atctatttac ccacccatcc 50820
catctttctt tcaatttaaa aggataatga ttttagtcac gattatacat aaacccatta 50880
ccataggcaa taaacaatgg ggcaaaccat tggtcccata gttggagtgt ggtctgaagt 50940
gtgttttggt ggagagagat ctatgtctgg agatagctaa catggatttg gatcccagat 51000
ctgctcctac ctgttgctgt gcctgtgacc aaatcatgtg atctctctgg tttcagttta 51060
cttgtgaata aagtaaatac cttcatcaac acctgttttt gaatacaatg tttttctgta 51120
atttttgctt cttataatgt tataatgatc atccttacat ctaaatcttg gtttacattt 51180
tcatcaattc ttttggaaag attggagaag taaattttgg agatgtatgt cggctattaa 51240
aaatgtttaa ttttttaatt aaaaattaaa acgttgaaaa atcctgatgc aaaataaatg 51300
cattatgctt agtgaactct tctcatttcg aagtttattc accttcttgt ttttgcaagt 51360
ttcctgaaaa atgcatataa agtcactaag ttagcagaac tttataaaat tatataacta 51420
tatataatct tttgatatca gtgaagccag ctgatcctat agaaataatg taggaattat 51480
aatcactagc acataattta agagtcctgt ggtcttattc atgttattta ccctctctga 51540
atcttacata tagtaagagg gttattatac ataatatgtg tacatgtata caggtaagta 51600
agtatatatg cttatgtgta aaagcagagt tattgtgaga gtcaaatgga aatgtgaaag 51660
tactttgtag ttttttatta ctattattaa tttttaataa aatggtaaca ttcatttaat 51720
aatcattagt tttaacttca gattgtactg gatttcctct agtatttctt aagattagtg 51780
aataaagtat ttctcctaat aaatatattg actactgtct ttcgatcaaa catattaggt 51840
atatttttac agtagcatca ggcagtgaaa atttgaagct ctttatagag gactgattta 51900
tgatgaaaag gaataacatg aacaaatgga attatatgaa gcttccccag aaatatctaa 51960
gaggggccaa ttttaagaaa tatctgactt ctttttcatg gacatttcaa aataaaccta 52020
actcatatgg tacagttttt aagagggaaa agaaaaaacc atctgagaat ctctggaatt 52080
ctgccgaaag tatcacttgg cattttattc taccttctgg atgcagttga ttgacagtag 52140
tgttatgatg ccaggggtat agtgactaga aaaagaaaac cagggaattc agtgttcttg 52200
ctcatgaaga acagcttggt tctttaaaaa caatgagatt ttgccacccc atctcacaaa 52260
cctatgattt gtgagaacaa tcccttttgt gttgcaagac ttttacattt ctcttcccac 52320
actatattag aagaataaac attgcttcat aagtaccgat tgatagtctc atttcatatt 52380
tttaaaatag agttacttta aggttaaatt tttcatgtag attaaaatga ctaagtaacc 52440
attcacatat ttcaaataaa atatattttt actacaaaag gaaaataact agattcttaa 52500
gtgttatagt caagtgtaat tgagtaatat gaattctaaa tgaatttcta agatctgctc 52560
agctttcact actttaggaa ggaacaactt aagaaaaatt ttaataaaga tatctcttca 52620
cacacatggc agtgttgtac ttagagaaca tgacccaaaa ttttttatga ctgcatattg 52680
aattcctgat actcttggga agctccaaaa gcaccagtgg agtttccaga tgtaactgtg 52740
gctgcagacc cgccagtccc ggtgttggaa gggatcatta taggctcttg tgtgcagact 52800
catcttcaga cccagaggaa ttaaataact tgcccaaagt cgcacaactt tctcatggta 52860
ggttgggcac tagaataaat attgcttttt cttaagagtt ttagcctccg tattatgaaa 52920
tcttctatgt tctgctgatg atatctcctt tcttcatctg ttttctattt ttaagcaatg 52980
gaaatacaaa cttgcaactc cccatttcca acacaactta gaaaaaacaa tatttaaaga 53040
aaaaattaca ggcatctcat ctcctttacc tgacagatgc ttgatagtaa tggcctctag 53100
atagggatga catctaatat aaatgtgtcc tttcaagtca agctttctct gttcattagt 53160
agaaatattg tatatcaagt gtgcaaaaat tttcttcaac agggagcttt gtttccctcc 53220
ttttattata acaatctgag ctttgtggtc ccagggtctc ctagtgcctg tctttaggtc 53280
tgtttattca catgaagaaa gcatgtcata tagtattatc taagactcag gctgcttatg 53340
catgatgaca gaagggttcc caggcacaaa cattcatcca tgcattcatc catccaccta 53400
ttcatccatt gatttggctg ataattattg actactgttg agttgccctc agatttagtt 53460
tctgtccttc tgccatgggg aaatatgggg ttaagccaca acatactctt ctcttctttt 53520
tctgcacctt cttagtatat ttagttccat tttgtctagc cctgcctctg acttctttgt 53580
tgtacttcag gttttttatc attgaaagtt atttctggat catagatcat tctcttggtc 53640
actttgcttg ttcacttata aaattaattc agaaaaaatg acccacagta attaccgtaa 53700
atcacagacc ataaactata atactgtata ttgtattata gtacagaaat atttatactt 53760
taaaatgttt taaatataga tattataaaa agatatgtct catataagta atataaatac 53820
ttttttatta cctcttctct ccctattctc caggccagtg ttttaaaaat ccatctttat 53880
atgtccatcc tggaaaaaac tcatgatcat aaatgagttt ctcaatagag tttataagcc 53940
cacagttgaa acacaattgt cttagcatcc atttagttgt catactttta agatttaatg 54000
gcaaatatta tgttttgttt cttcaaaaga aatattttaa aattttagta aaggcagtta 54060
gagaaggtag agataatgga ctgtttaatc ctacttttca tcccacaagt gaacaaaaaa 54120
atgataaaac atttttccca aaatgtagct ttaactatac ttaaatttgg actaaaatgg 54180
gagatatctt ttctactatt gaaaagccgt gtctgtagat taatgctaaa atcgggtgta 54240
aaagcaaaat ttgtttggct tgattgccaa tggcccattc atttggctac agaaacaata 54300
gcacatagca acagataatg atgtgagatc acctagctca agtaagagtg tctgatccgt 54360
caaaaatata tacatcaaga ttcaaaagaa atgtgtgttt tctcaagtca tctctgtaaa 54420
aatacattaa atagaggaat agaagtttga ctttgaaaat acattgcaga cccaatccgt 54480
ctttcctatt ttctggtgaa aagtatcaaa tatgtggaac ctggaactgc tattctcctt 54540
cttaaaaatc tttcttaata ttctattgat aactggtgca agcctaactt tttgtcttac 54600
ccgattcttc tcacaccaaa gtgataggac cttcaggtag cctttggata gaagataaat 54660
aataatttaa ctattgatgg aagttagtat tagaattaga cttggaagtc tatggaataa 54720
aatgattcta caacaatttg tacttcagac attagtataa caaaacatgt ttgcccgtgc 54780
atgcggaaac aaccaatttc atgtggatgc ttatattcac aaaggagtaa ccacctgggg 54840
tttcccactg ttgctccaga gaaaactagc agcaggagaa cttctctgaa ggtatcaaga 54900
catctttaaa aaacacttgt taagtgttgg ttcagctaaa gcagggagtt ttcagttagt 54960
aatggctttt aaaaattaaa acaagtttag catgtaggtc attaaccttg aatcactgtc 55020
atgattatta ttaaccatct gttctcaaat cgaaagatat ttttcttttc tagatcacat 55080
ttattctcac attgctcaat ttcactatat atcaagacat gaaaactgta aaaatcacac 55140
cttctacatt attattttta ttgaaaaatt cctaatgaaa cagtgcgctc tgggatagag 55200
aaaggaacta actgacattt tgcttcttaa cttgttttta tgcaagttct aagtggtttc 55260
tggccatgta cataaaagac aaatatctgg aaaaaaaact agcagaagtc agttatttgg 55320
ctctatctac tttgagaatt atgttatata aatgttagga aattttttgt aatattctta 55380
tttagaaatg aaatataaaa agttttaaaa atatctaagg acagtataca gtcctaaagt 55440
aaagctgtta ggtaaatgct acacaatcct cttattacag agtcacttac ctgagaatat 55500
aagaagaggg cctcttgttt aagagtaaat gtgagctgca atcaggattc tgcactcatt 55560
tggacactta gttttgtttt tccatgactg gtgttgcctg ttactgagac acctacctgt 55620
catgtgacca cagcttatgt tacaatgtgt ctagtcagac ttagagatgt gtgaaagagc 55680
agtacctaga cgggaaacta tgggtctata aaggttttgc cttcttgggc ggagttcaaa 55740
ctaggaagcc acaaaacttc cagttgcatt ttcacagatt aatgaaatat attttacact 55800
tttcctgaaa gatattttat ttgtgcaaac cttgttacaa agtacagcca gttgattaat 55860
cgatgaagtg atttgtagtg gattcttata ttttgtgtaa gggtatatgt gaggccctat 55920
atatgaggct ttctatataa tgaagtataa ttcagttcag catttcaatt cagcaatcac 55980
ttattgggcc tctactcagt tgccttcagg gctttataat ttaattgata aagggaggtt 56040
aattaattaa ttataacaac agatcgctta atagtgtaac tactaattta attaatgaca 56100
aataacaata cattaaaaga aatgcattaa taaaaataat atattggtgt tatagacaat 56160
aattttctga ttaactttat tattattatt tcaatagctt ttggggagca ggtggttttt 56220
ggttatatgg agaagttgtt taggtatgat ttctgagatt ttggtacact cataacctga 56280
gcagcataca ctgcacccaa tgtgtagtct ttcattcctc accttcctcc cacccttccc 56340
ctcaagtctc cagagtccat tatatcattc ttatgccttt gcatccttta gtttaggtgg 56400
cagttataaa tgagaacatg taatgtttgg ttttccactc ctgagttact tcacttagaa 56460
taatggtctc caactctatc tacgtagcta caaatgccat tattttgttc ctttttatgg 56520
ctgagtagta ttccatagca tccacacaca cccccctatg ctttatatat atatgtaaat 56580
atatcacatt ttctttatcc actcattggt tgatgggtat ttaggctggt tccatatttt 56640
tgcaattgtg aattgtgcag ctataaacat gcatgtgcaa gtgtcttttt catataatga 56700
cttcttttcc tctgggtaga tacctaggag tgggatcgct ggaacaaatg attgttctac 56760
ttttagttct ttaaggaatc tccataactt ttccatggtg gttgtactag tttacattcc 56820
taccagcagt gtaaaaaaat gttccctttt taccacttcc atgccaacgt ttattttttt 56880
attttttaat tatggcaatt cttgcaggag taaggtggta tcacattgtg gttttgattt 56940
gcatttccct ggtcattaaa gatgttgagc attttttcat atgtttgttg gctgtttgtc 57000
tatcttcttt tgagaattgt ctattcatgt ccttagccca ctttttgata ggattatttg 57060
ttttttctta ctgatttgtt tgagttcctt gtagattctg gatattagtc ctttgtcaga 57120
tggatagttt gcagatattt ctcccattct gtgggttgtc tgtttactct gatgattatt 57180
tcttttgctg tgcagaagct ttatagtttt aggtcccatc tatttatctt ttttgttgtt 57240
gttgcatttg cttttggttt cttggtcatg aactctttgc ttaagccagt gtctagaaga 57300
gttttaccaa tgttatcttc tataattttt aaggttttgg gtcttagatt taagtctttg 57360
atccatcttg agtggatttt tgtataagtt gagagatgag gatccagctt cattcttcta 57420
catgtggctt gccaattatc ccaacaccat ttgttgaata ggatgtcctt tccccacctt 57480
atgtttttgt ttgctttgtt gaagatcagt tggctgtaag tatttagctt tatttctgga 57540
ttttctattc tgctccattg atctacatgt ctatttttat agtagtacca tgctgttttc 57600
ctaactatag tcttgtagta tagtttgaag ttgggtaatc tagtgcctcc agatttgtta 57660
ttttttgctt agtcttgctt tggctgtatg ggctgttgtt ttgttccatg tgaattttaa 57720
gatttttttt cttgttcttt gaagaatgat ggtggcattt tgatgggagt cgcattgaat 57780
ttatagattg tttttggcag tgtgctcatt ttcacaatat tgattctgcc aatccatgaa 57840
taagggatgt gttttcatta gtttctgttg tctgtgattt ctttcagcaa tattttgtag 57900
ttttcctgta gagatcttcc acctctttgg ttaggtatat tcctaagcat tttttttttt 57960
tgcagctgtt gtaaaaaggc tcaagttctt aatttgattc tcagttttgt tgctgttggt 58020
gtatagcact ggtactgatt tgtgtacatt gattttgtat ctggaaactt tactgaatta 58080
acttatcaga tctaggagct ttttggatga gtctttaggt tttctaggta tacaaacata 58140
tcatcggcaa agagcaacag tttgacttcc tctttagcag tttggatgct ctttatttct 58200
ttctcttgtc tgattgctct ggctaggatt tccagtacta tgttgaatag aagtggtgaa 58260
agcaggcatt cttgtcttat tccagttctc gggggaaatg ctttcaaatt ttcccccgtt 58320
caatataatg ttggctgtgg gtttgtcata agtggctttt attaccttaa ggtgtgtatc 58380
ttatatgcca gttttgctga gggttttaat cataaagcaa tactgaattt tgtcaaatgc 58440
tttttctgca tctattgagt ttatcatatg atttttgttt ttactcctgc ttatatggtg 58500
tatcacattt attgacttgc atatgttaaa gcaaccctgc atccccggta tgaaacccac 58560
ctgatcatgg tggattatct ttttgatatg ctgctggatt catttagcta gtattttatt 58620
gaggattttt acatctctgt tcatcaggga tattggtctg tagttttctt tttttgttat 58680
gtccttttct ggttttgata ttagggtaat actggcttca tagaatgatt tagggaggat 58740
tccctctgtc tctatctttt ggaacagttt caatagaatt tgtaccaatt tttctttgaa 58800
tttctgatag cattcacctg tgaatccatc tggtcctaga ctttttttgt ttcctgacat 58860
tttttctatt attgtttcac tctcactatg cattattggt ctgttaataa tttctatttc 58920
ttcctgtttt aatctaggag gtttgtatat atgcaggaat ttgtccatct cttcttggtt 58980
ttctagtttg tgtacgtaaa tgtgttcaca gtagtcttga ataatctttt ttatttctgt 59040
ggtatcagtt gtagtatctc ccatttcatt tctaattgag cttgtttaga tcttttttct 59100
tgttttcttg gttaatcttg ccaatggtct attgattttg tttatctttt caaagaagca 59160
ggtttttgtt tcatttatct tttgtattgt attttgtgtt tcaattttat ttatttattt 59220
atttattttt atttttattt tttgagatgg agtctcactc ttgttaccca ggctggaatg 59280
caacagtatg atcttggctc actgcaacat ctgccttcca ggttcaagtg attctcttgc 59340
ctcagctgcc cgagtagctg ggactacagg tgcctgccac cacacctggc taatttttgt 59400
atttttagta gagacggggt ttcaccatgt tggccaggca ggtctcaaac tcctgactta 59460
tggtgatccg cctgccttgg cctcccaaag tgctgcgatt acaggtgtga gccaccacac 59520
taagactcaa ttttatttat ttctattctg atctttgtta tttcttttct tctgctgggt 59580
ttgggtttgc tttgtcttgt ttttccagtt cctagaggtg taagctcaga ttgtctattt 59640
gtgctctttc agactttttg atgtagatat ttaatgctat gaactttgct cttaacatgg 59700
cttttgctgt atcccagagg ttgtgatagg ttttgtcatt attattgttg aattcaaata 59760
tttttaaaat tttcatcttt cttgatttca ttgttgaccc aaagatcatt caggagcaga 59820
ttattcgatt tccatgtatt tgtatagttt tgagggtttc ttttggagtt aatttttaat 59880
tttattccac tgtggtctga gagaatactt gatataattt tgattttctt aaatttattg 59940
agacttgttc atatggtctg tcttggagaa tattccatgt gttgatgaaa aggatgtagt 60000
tgttgggtag gattttttgt aaatatctgt taagtccatt tgttctaggg tatagtttaa 60060
gtccatgttt ctttgttgac tttctgtctt gatgacctgt ctagtgctgt cagtggagta 60120
ctgaagtccc ccactattat tgtgttgctg tctatctcat gtcttaggtc tagtagtgat 60180
tgctttataa atttgggagc ccaagtgtta gatgcatata cacttaagat tgtaaatttt 60240
tcctgttgaa ctaattattt tatcattata taatgtctct ctttgtcttt tttaattgtt 60300
gttgctttaa aatctttttt gtctgatata agaattgcta ttctttctca ctttgagttt 60360
ccatttgcat ggaatatctt tttccacccc tttaccttaa gtttatgtga gtccttacgt 60420
gttaggtgag tctcttgaag acagcagata cttggttgat ggatttttat ccattctgcc 60480
attctgtatc ttttaagtgg agcatttagg ccatttacat tcaacattag tattgaggta 60540
tgaggtactg ttctattcat catgatagtt gttgcctcaa taccttcttg ttgttgctgt 60600
tgttaattgt gttattattt tatgggtcct gttaaattta tgctttaagg aggttctatt 60660
ttgatgtatt caagttactg tttcaagatt tagagctcct tttagcattt ctcagtgctg 60720
gcttggtagt ggcaaattca gcatttgttt gtctgaaaaa gactttatct ctctttcatt 60780
tatgaagctt agtttcactg gatacaaaat tcttggctga taattatttt gtttaagagg 60840
ctaaatatag ggcccaatct cttctggcta gcagggttta tgctgagaaa tctgctatta 60900
atctgctatg ttttctttta taggatacct gatgcttttg cctcacagct cttaagattc 60960
tttccttcat cttgacttta gacaacctga tggctgtgtg cccaggtggt aatctttttg 61020
cattgaattt cccaggtgtt ctttgtgctt cttatatttg gatatctaga tctctagcaa 61080
gactaggaag tttttcttga ttattccctc aaataagtcc ttaatgaccc cactatataa 61140
catgaaatat ctgttattgg tactgaggtg ctggccacaa acaattctgt gtgtcctgaa 61200
aactcttcag aatattcgtc atctttagca cttgttatct tagtgtttgg gcttggctta 61260
gagtgataca tctcataaca gggcaacaga aagaaccagg aaccaagatt tatataacat 61320
aagtcagtaa aactagaggc accagaggtt tacatttaca ttaggttaca ttttctaaca 61380
ggtagcaaag cacatgaatg aagttcagtg gaaggccttc ctcaggaatc cagtaaaaac 61440
caaacataca cacacacaca cggacatccg tgaggcagga agggatgtcc actatagtac 61500
agacaagcat cctggaaggc catcaaggag taggtgggtt tcagttgcct caggaatgtg 61560
gcatggaccc aaactaagtg agtacagata cttgtcattg aggagaagat tcaaaatagc 61620
atcctaggtg taaaaactga ggcacctggg gcaggggaac taggtctctg gaatgttggc 61680
ttaaaagcac ccctctcagg aaaggcctca tatgccatgc agggggttat atatgtgttg 61740
tgggacacag atggcaagga gataattcta tgcaccaggc tccactacta acaggtaaac 61800
agaccaacat taacagagac ttaggtaaaa aggtaggtgc ccagtggtca gttctcaggc 61860
acttccaaga tgcacctaac agaaatgtaa cttggtgtct attgtgtcct aggtctaaca 61920
actgaagaga agtgaattag tacctcttgt ggacagagaa acaggggcag agacccatta 61980
caaagctgtc tcagataggc atttgaagct gtttaagtat gtagaggctt aagtcaggct 62040
ggttctgaaa tgtgagagag ggttaagctt catgggaaat cagcagggta gtttgctatt 62100
ttttattata accaatctca caatagtttg ggacatcaaa tatcaaattg ttgggaatat 62160
ttatccatat tagtcttttt gccactaata tttaaaaata gtttacaata tacaacaaaa 62220
agttgtaaaa tttccatctc cacttaatcg atcttatgta acccatacaa tacatcaaat 62280
gtcctttccc cactttatgt ttttatttgc tttgtcaaag atcacttggc tgttagcatt 62340
tgggtttatt tctaggttct ctattctgtt ttattggtct gtgtgcctat ttttatacca 62400
gtgccatgct gttttggtga ctatggcctt atagtatagt ttgaaagcag gtaatgtgat 62460
gcctccagat ttttcttttt gcttaatctt gctttggcta tgtgggctct tttttggttc 62520
catatgaatt ttaggattgt tttttctagt tctgtgaaga atgatggtgg tattttgatg 62580
ggaattgcat ttaattgtag atttctcttg gcagtattac ccaggctttt cttattttgg 62640
caccctgtgc tgctgtctcc ttttccttct ttctgcttct cttaaccaac tgttacctac 62700
acttcaatac tttctgaggg caattcatcc tccagtaagt ctccctgaat cttctcttcc 62760
ttccctggct tattatatat ccttcctctt ggttcccata gcacctatgc acacttctgt 62820
cattgcactt gccaatttgt tttataatga tctgctcatc tgtctcctca cttagactat 62880
gagctcactg agagcaatgg ctgttgcatt caccttatat cctcaacacc attctgaagg 62940
caagagaaag aatacccaga ggtggagctg ggaagctggt tgtccaagta gtgaatgact 63000
ctagtttgaa ttgaactcta tagccagtgg gcaatgtgga tgtgttgaca gttttttaac 63060
aggggactag tgaaaacaca ttttgggttt agaaaaaatt gcaagtctga tgacatacat 63120
aggagaagag attagagata ggaatttcac ttcagaaatt taaccacaag agcaagtgac 63180
agatcacgga agtctgaacc agactataaa tgtgagaata gagaaaaaag ttaacaattt 63240
gggtgtgaaa gggcgaggga gagaggtgtg aagaatgact aagtgtggat ctgtttttaa 63300
ggattgaatg gaaatttgag cattttagct aatcaggcct aatattgagc aaagcaaaac 63360
tcttgcaaat tgttatttca agtgtgggct gagaaaatga aaaaatataa attctcacgt 63420
tataacctct tccgtgtgtc tgatttgata gaatccagcc ccattgcctc caaattccat 63480
tgcatcttag accagcaaac acaagtgaat tctacttaac cccagaattc tgtatgaaaa 63540
tcttactgcc tttttttttc taatcatgtg tcaaagtgtg ggaagaactt ttatttatgt 63600
tttaataaat tgtcagtata accattttta cttgaaaata ttataatttt tcaagtaaac 63660
aaattgtttc tctaagttga aaattttatg atggaataaa agtatttttc ctcaaaacac 63720
atagaaattt tacaacaata ttttagagtt aactaaatgt ttctttagta gtttagtcac 63780
ttaaaaagtg atatgattat gaaaatactt aaactttgtc ttttaactat ttctaataat 63840
gctattggta taatttcata tttttatact gatcttttct ccaaacttta gtaaaacata 63900
cttctgtaaa cccctgccca caaaactgaa gtccacattt acttctgaat gactgataag 63960
tttgtaaaag tatgcatgaa tttcgttatt aaattaaagt ttttattata ttttatgcac 64020
aatggtataa attattaaat taattttcaa gcttatagaa cattgataaa gattgtcatt 64080
agaaaaccct gagttgattg ttatacatta cataaccttt cattggtgga ttagtgaata 64140
tgttataggg tgaccatgaa tccaaagaat caaagctggc tacagcaaac agagggtcaa 64200
aaggatatgg aactatgcat gatccagcaa aacactcaat atctgttttc ctggaatgtt 64260
aaaagacaaa gaagaaaact tggggaacac tagatgcata tagttctggt tctttaagaa 64320
taaaaatatg ggccgggccc ggtggctcat gcctgtaatc ccagcacttt gtgggaggcc 64380
aaggcgggtg gatcacaagg ttaggagttc aagaccagcc aggccaacat agtgaaaccc 64440
tgtctctact aaaaatacaa aaaaaaatta caaaaaaaat acaaaaaaaa aaatagccag 64500
gtgtggtgac aggcacctgt attcccagct acttgggagg ctgaggcagg agaatcactt 64560
gaacccggga ggcagaggtt gcagtgagcc aagatagtgc cactgtgctc cagcctgggt 64620
gacatagtga gactctgtct caaaaaaaaa aaaaagaata aaaacaagaa tggtcagagt 64680
cctagtacct tgtccagtgt agtgctgcct tgagattgca ttgcaatctg tctgagagat 64740
agtaaaagaa agtgatacct tccttagccc tgtttctctt tagactatgc tttcccctct 64800
ccaagttaat atctctcagt ctaaagcctg ggaaaaggtg ccaattttgt ttttctttct 64860
tcctcacacc tcctagaagt tacactggga cactattact tttttccagg ctttggccat 64920
gtgtattgtt ttggagagtc aacttccttt tttctttcat tctgcaaata gttttgagct 64980
gtcactctgt actaggtgct ataaaactta caggtgcatt ttacatgcct atttcctata 65040
ggccacgatt taacaaaatg ttcataaatg agaattagga gtgcatgtat tgaatcacca 65100
cacattaact gaacagcttt cattggccag agactatatt gacagtggag attcaaagat 65160
aaactagaga aatctcatgc ttaaataact ttctataata aattatataa gagaagtagg 65220
ttcagggatc ttgggagctc agaagcagga tgagttaaac aaaagttgga ttttgccttt 65280
agcttggttt cattatcctg aaggaagagc ctgaaatata gtgtagggtg caagtagtat 65340
atgtgggtgg caatctcggg aaacaggagc atgtgatgaa taaggagaaa aagccaatat 65400
aaaggtactg cattgagggc aatgagggct ctaattctct gcaccttctc aagcattgtg 65460
cagattggtt ttctggatta tcagcctgaa ggacaaaacg aagaaacagc cattagctcc 65520
tgtctcccat tgtctgagag ctgccactag gatattaact tcctgaaatt ctgcagaaat 65580
ctcctcttac tttggcactg gagatgccca tacgcagaaa gcaaaaaggc acagcatatt 65640
taaggaagct cataagaaac agtgcatcca gaagtggcga gaattggagg aatggacatg 65700
agactctaag aaccagcgcc tttgatgttc cttttgatct gttatgtagc tcttcttgta 65760
cacaggtgag caaaggcatg ctggacaaat ggattcacat gtgctaaagc atggggcaaa 65820
aaccacatat taattcagga aaagacaaga tgcgtggccc tctctgtctc tgtctaaggg 65880
tgaattaaag aggggatata tgtacagagt ggcagggcag gacttgagat aagaaggcta 65940
ggtgggtgct ctcatgctag tagcattata gtacaggtga tgagaagctc ctgaagaatc 66000
atcttaacat ttgtatttta gagcaacagt attgagttct gacttagaga cagcaaaact 66060
aaagacagaa agactatttt gattattaat gatgtagata taagaatatc gtcaatgtga 66120
actaaagcat gaagctactt atgatatatc attaaaagga tttaactgat tggagacaaa 66180
cgagagggat ggggaaaaga attcatttgt ttttagttgc tctttttttc ctacttattc 66240
ctttgttccg agtgtgaata aactttgtaa acttttatac taaaacattc tgctcattca 66300
tacttatttc tttgatgaaa caaggaaacc cttgtatagt tataaacgtg tgaatcaatt 66360
taaatattag gaaatttttt taaataaagc tagttttctg aaggggaaaa acttggttca 66420
attttttgct ggcaatctgc tttgtgattt ttgaacatga tatctacatc tagactcatg 66480
ttttgctagc tggaattttt tttcaaatta acgctaccat tattatatgc tttactattt 66540
agcttttgca gccttggaaa tctatgatta atacaaataa ttctctatgg caattttaaa 66600
aatacatgta aaagccttca atctacattg ctactgtgtc gtagcacaaa aaaagaaaat 66660
gtgatcaaat tttaataaaa tctacaattt attcccttct aaatacagtc ctagctcagg 66720
agaaaggaag ctatttgtat ttttcagaat caaatttccc taaatgaata tagagaaaga 66780
attataactg aaatattgtt gaaacagtgg tcatctcaaa tctgaaggtc attccaaaaa 66840
agtttctgag ttttcattgc ctcaatctaa aagttggcct ttttggtaat agatgaaagt 66900
aaaataattg aaagggtctg ttgcagtttt ggaatatctt gaaaatatag tagagtgaag 66960
ccttcttccc ttaaataaaa gacaagttgc tgattgtttt ctttctagcc agataagaat 67020
aatgccttct ttctcttgtt agtcttaaca cctcacttgt tactatgtgt cagaaaggcg 67080
agacaccata aatggagata ctactgatgg aggtcatctg acatggggct ggtaggcagt 67140
gggaagactg gtatggacac aggtggctta ggggttgggg aatgatatgg aactaaggaa 67200
atgataatta gcagaaccca gtgtgcatgt gtgtgcattc gtgtgtccgt gtatgtgtgt 67260
actgtagcac aatgcaagaa agaaaaaaca aggcagactt ttcataattt cagggataaa 67320
taaatccttt atcacttcat gtagaatatt ggctacttgg aggtatatct aaacgtaaat 67380
atataactat ataactacat gctaattaaa aacatacaaa gaagaagtgc ctaaagaatt 67440
acaacagaaa gtggcatagt gattattaga gttaatataa tataaataag gccaggcatg 67500
gtggctcatg cctataatcc cagcactttt ggaggtcaag ttgcagggat cacttgagga 67560
caggggatag agacaagcct agccaacatg gtgaaaccca tctctactaa aaatacagaa 67620
attagctggg tgtggtgatg ggcgctggta atcccagcta ctcaagaaac tgaagcagga 67680
gaattgcttg aacccggaag ctggggctgc agtgagccaa gatcgcgcac tgcactccag 67740
actgggtgac agagaaagac ccggtctcaa aaaattaaaa aatagtataa ataatatttc 67800
aaaacacaag tctgttaaga taaaaggtac agaggaatgg tgagatgact tttttatttg 67860
tgtgataagg gactgttttc tgtgattgtg agaaagacca ggagttaaga aaaagtggcc 67920
atcaataaat cagccactta tggggaagaa ccataaacca ctctcagatg aaatacaaat 67980
gcagtcatta tttaatatta ttggaatatt tgtattagtt tttggtatgt gctgctagtg 68040
ctggtacatt ttagtagtca attaatattt tgttaatctt aatttctaac taaattccag 68100
agtgaaatgg aaataataat gaaaaaattt tatttacaaa acagattttg tttttttctg 68160
ttaagaatga tacacagttg tccttcagta gccatagggg attggtttca ggacctccct 68220
tgggtactaa aatctgcaga tgcctaagcc cctgttataa aatggcttag tatttgtata 68280
taacctatgc acatcctctc atatactttc aatcaggggt ccccaacccc agggccatga 68340
ccagtactgg tccatagcct gttaggctgt tcgataccag gctgcacagc aagagctgag 68400
ctcctcctcc tgtcagctca gtggtggcat tagattgcca taggagcacg aaccctattg 68460
tgaactgcac atgtgaggga tctaggttgt gcgctcctta tgagaatcta atgataaatg 68520
taatgtgctt gaatcatccc aaaaccattc cccttcccct caccatccct gtccgtggaa 68580
acatttcttc cagaaaacca gtccctggtg ccagaaaggt tggggactgc tgctttaaat 68640
aatctctaga ttactgataa tgcccaatac aatgtaaatt ctatgtaaat agtttttata 68700
ctatattgtt tagagaataa tgaaaagaaa aagtctacat gttcagttta agtgttgata 68760
agtgtgtaga gaaaagggaa cccttgtaca ttgttggtgg aaatatagat tggtgcagtc 68820
attatggaca atagtacgga ggttcctaaa gaaattaaaa ttagaattac ctaagaccca 68880
gcaatccctc ctctggatgt acccaaagga aataaaatca tcacctcata aagatatctg 68940
cactgctata ttcattgcag cattatttac agtagccaag atatggaaac cacctaggta 69000
tgtgttggtg catgaatgga taaaagaaac tgtggtatat gtatatacaa tggaatatta 69060
ttcagcctta aaaaaggaga agaccctgtc atttgccaca acatgcatgg acctggagga 69120
tattaagctg tgggaaataa gtccaacaca catccacaca caaaattgca taatctcact 69180
tatatgtgga atctaaaaag aaaaagttca aatataaagt tagaataaaa cagtggttac 69240
cggccggatg tggtagctca cgcctgtaat cctagccctt tgggaagccg aggtgggtga 69300
atcacctgag gtcaggagtt caagaccagc ctgaccaaca tggtgaaatc ctgtttctac 69360
taaaagtaca aaaattagcc gggcatagtg gcaggtgcct gtaatcccag ctactcaggc 69420
agttgagaaa ggagaatcac ttgaactcag gaggcatagg ttgcagtgag ccgagatggc 69480
gccacttcac tccagcctgg gcaaaagagc aaaactctgt ctcaaaataa aaaaacaaaa 69540
aacacagtcc acacactggt taccatgagt gaggtggcag ggaggagatt gggagatgta 69600
gatctaagga tacaaagtag cagatatgta ggaggaacta aaaagctgac atgcaggatg 69660
acaactatag ttagtaatag tgtattgtat tcaggatttt tgctaattga gtagattata 69720
gctgctcttg ccacagggga aaaagtgggt aactacgtga gatagacaat ggatgtgtta 69780
atttttgtca ctataataac cttttcacca tatacattca tcttataaca gcatgttgtt 69840
tactgtaaat atatacaata aaatttattt ttaaatatct gagtatgatt tgatgatttg 69900
tgaaaataga gtgaattata ataattttaa atgtaagtta atgttattag aaaagaaaca 69960
gaaagaacat accacacaga aagtctgtct gaaggatctt tgttttctcc accaatacaa 70020
gtgttcattg attcagaggt ggattatgag atatgaccat aaaacaaaaa tttcaaggga 70080
aatatatttt attcaatgaa aaattctcaa cacaactgtt atatgccagt aaacactata 70140
tcttttaaat aacaggtcat atctattata tttaaaattc aaggagagac tacattagag 70200
atgctattag atcaacttct aatttcaaag atttctaaga tatggaacag ttactcctta 70260
tacaaattaa aaaagcaaat gctgaagaaa ttcagctaca tggatacacc atgaggtgga 70320
aagatgctcc ataactctta gttaaactgc actaattaca cataaaagga aaatgtttca 70380
tttcactgta atttggaaac caaagaaaga aaagactgaa tttttacata ctgttaaaga 70440
gattgcgtat ctgttctaag tttaagacag aggcaaaatg tattttattc atttgtcctg 70500
caccgtttag aaataaaatt caacttcctt ttaatttttt ttaagaataa aaaactcagt 70560
ctaaggaaag tcttaaagtt ttcattttaa gtgatccact gttctagaag tttaatattt 70620
tgtttaaaat gtttatgttc tgtattccac caagtctagt tttaaaacaa aacaaacaac 70680
aacaaaatac ttctctaact tggagtttaa ggtgaaagaa accaattacg tggtttggaa 70740
atgtcacact tttcatctct tttttaaaaa aatttttaat tcaggacaga aattgtatgg 70800
atttagtgta agtcttggga tctcacaagt gtcagtattt cactctcctc catatcttga 70860
tagcaataac ttgaaatagg atctcagtag ctcaagcaat actgggctct gagagttggt 70920
taaaaattat ttggctgagc gcctgttgct gagggaagaa ctaatctcga gcatattttt 70980
ggagccaaat accaaattgt ttgtgcttag caacacagca ccaggcttgc ccttcagaat 71040
gattctagac caaatgccag aaatgctctg gttctgacta cagagttcta ttcacaaatg 71100
acaggaggca agaggtcctc ctcactttca gaagaaaggt cctttgcttt cttagtcaat 71160
ggtaggaaaa ccattgtggt tttcattgca ttacataatt tttaaggtga ttacttcaat 71220
aagaagtgct ctgtgtatat gtgtgtttat agacgcattt tttaaacact ggagaatttc 71280
tgaaagtagt acaaaccttg taatgtcaag tagatgtggg aaaaagggag tttacaacat 71340
tctctcctga cattgctctc ctttggcatc tgcattttta aaatgttaaa aatgtttaaa 71400
aacgtgtgct taacacttaa tttggtgata gttgctgtta ccaaggcaac tctgtaactc 71460
cacccagata aaaataaatc ttgaagatga gtttctgtgt ctctgagcaa atatttttgt 71520
gaatagtaga agcagagaaa gttaaagata cctgagcttt tgatctttac tagttttata 71580
gatatgttta tagttataca tttttattca tacattttag ataaataact ttgtaaagca 71640
attgattctt cttgtaaaaa tcaagtatat tcttaataga ctgataaact ttcttttttt 71700
gagacagagt cttgctctat tgcccaggct ggaatacagt gccatgatct tggctcactg 71760
caacctacct ctgcctcctg ggttcaagca attctcctgc ctcagcctct tgagtagctg 71820
agattacagg tgcatggtac cacaccccac taatttttgt attcttagta gagatggggt 71880
tttgccattt tggccaggct ctgagaaact ttttaaggtc tcttttgcag ccagctattt 71940
gtctacctta tttcattctt aatctcacta gccaatattt tttctgttta agtgctttca 72000
gcaaatatta aatgcttgtg ccttcagtct tatcctgtgg aaacactggt aatgacaaaa 72060
acacatattt caacctaata tacaatagaa acagaatgcc agttattcat ggaggagaag 72120
aatagacttc tgtatttaaa ataacatttt gctctgtgtt ttaaaatcat tcttccttca 72180
tcaattgtaa gcatcttgac tataatttat acacctaaag ataaataatt cagtagcaat 72240
gataactgaa aacaggacac atacaatgaa ctagctaaat taccatacat tctcatccat 72300
ttcaaaaata gctctgtact tttttcagat tttgttagaa gaatattcaa tacaaatttt 72360
tattcaatga acacttcaga tgtcaagatt gttacccaca tggacaacag taacctaggt 72420
aaagattctg cagccaggcg tggtggctca cacctgtaat cccagcactt tgggaggctg 72480
aggcgggcag atcatgaggt caggagatcg agactatcct ggctaacatg gtgaaacccc 72540
atctctacta aaaatacaaa aaattagcca ggtgtggtgt catgtgcttg tagtcccagc 72600
tgctcgggag gctaaggcag gagaatcgct tgaacccggg aggtggaggt tgcggtgagc 72660
cgagattgca ccactgcact ccagcctggg tgacagagcg agactctgtc tcaaaaaaaa 72720
aaaaaaaaaa ttttatacct gggctctgtg ctcaccagca gaaggggtaa catggcttct 72780
taggacaacc ttacttgacc atttacttct ttgacactag gggtattctt agatcagcag 72840
gtccttccct ccacttatgc acatgaggct cacagagagt ctgggaggca gggaatttat 72900
gattggaaac agtatacttt ttatctaaga aattattaat gtcactgcat tcaagtgatt 72960
aacaccatca atatcttcaa gactaagggg attacatgat gtgtaaaatt agaaaactgt 73020
catctactag tggctaggca ctttaattat attaagcatg caacaagaga actcttcaaa 73080
tgaatccatc tctcctctgt attatttcca acccttggat ccccatctgt ttctgcagac 73140
aacagctatg ctgctgaatg tcttaatggt ttgctgcccc aactagcttc aagatactgc 73200
aggtcaagca tagcatctta ctcttccctg catctccagc acctctcaga atgttggtca 73260
catagaagat gtttgctgag gagttgaata agaatatgta caagggacac aattagcatt 73320
gtttaaaaaa gatgtaacaa gatagggtaa aggaaagctt tggaggataa atctttagaa 73380
caatcaataa tatcttctcc tctgttggtt agttgccctt caatctcagc cactgaatca 73440
aatacaacat aattactatt ctgatatgtt cttgaatcga atatccaata ataagatatt 73500
cggatgcata gccatgtcta atatcaaagc ccatgctttt cgctattatt gtactccata 73560
cattagcttc caaatttatt tgcaatccaa atattaaaag caagtcataa gcttagtatc 73620
gccaatgtga tactaagtat ccacttacta aactttattt tcaaaatgtg gttttatctc 73680
agtttaatga acacggcatg ttttaattta cactttcata ttatatagta agggcgtggt 73740
tacagatatg ttaatttcct gtgctgcttc acaatgatgg aacataatag caaatgaaac 73800
tgttaatttg cagataccca taggcctttg gtgtctgaat agaaataaac acacctacaa 73860
ctgagagagg aagcatgtga agcattccag tgaacagagg ccatttattc agtcacagac 73920
acaggagaaa aacaacaatt aaaaaaaaat ctctgatgaa aagttcataa aaagttcact 73980
cagtttaagc atatgtccta taactactta aaatagagtt cttcttaaat atcattcttt 74040
gctgttttta gatttcttct gcctgtatca aattaataga acacagcata cttttaattt 74100
gctctggttt cttagtgggg catttattaa acacattaaa acaatagtct cagggtttta 74160
ctgctgatgt taaagttctg ctttcctact taccaactgt gtcatcttaa ggcacatact 74220
ttgcctctct ctcaaatctc ccaaatggag aatgataaga atacgtacct caattaaaga 74280
agctataaca agtagaatgt ttggaaaagt gccgggtaca ccataagccc actatgagta 74340
ttggattgta ttacctctga aagctgcaga atggaattct caaagttata tgtccctaaa 74400
atcctcttaa gtgacagaaa tggagaaatt agcagtctgt ctaagagagc ttttctagag 74460
tctgggcata tgtttttagg acaagacagt tcagcttcag cttaaaatga gagagcacgt 74520
ctgtgtcctt actcctgggt gccaggtttc ttgtccccat cttaagacaa ataattttgg 74580
tggagaagag gcagtctctt tgatttcgct ctaaaaacct tttctggagg aggtagacac 74640
tctccacccc cgttttgaga ctcatgcagc tgaggatgac tggctgagta caagcaattg 74700
ttccttctaa gcagtttcaa ttcttataac ttgtggagat attcttaagt ccaggggatt 74760
ttgtgtatgg tggattttta ttacaaagtc ctgtacttca taggaacaaa ataattcaaa 74820
gtcaggaacc agatcaaagc cacaactcag atatggcacc ttgagaagtt catttgtatt 74880
tcacttgcat aaaaaccctc accactgcta tctgattttc acaaatcatt caacagctat 74940
ccatgaagca cccactgtgt gtctggtctc tgtgtcagtc cctggcttca tgtgtctttc 75000
cttctgtacc ctgactcccc aactcatgaa cacatgaagt aaaaaaatga aaatcttttt 75060
ctgacctctc ttcaaaatca cttttttcaa aacaaacacc tctcacctgc tcatcctcca 75120
gccagtaaat cacaggggcc tagaaatgtc acttacaaat attttctgat tctgtccctc 75180
ccttcaagct tgccaacatt atcacagttt agggcctgct catctttccc ccaatctcca 75240
attagatctc tccacaatgc aattctgcac attccctgtt acaacccttc aattatttcc 75300
cagcccatcc aaaataaaat ctaagcctct tactaacaca ttcaggaact ctgtggccta 75360
cggttttcta cagactaatt ttccagcagt tgacttccag tgcaagtgaa aacctagtgt 75420
catgcctgca tgatagataa atttgaagct gaagagccca aatgtataga ccatgccatg 75480
aaaggtttat agtcatgaca cagtggccct atagtacagt gcttgaagct ggctctctac 75540
tgtcagacag accacttgcc agccatgaga cctggggcaa aatgccttaa tttttatgtg 75600
cctcaagttc tcatgtgaga tgagaataaa aattacccct atttcataag atttgataaa 75660
gtgtttagca taatacctca taacaattgc aattcagtgg tggttattat tataaagaaa 75720
agatgattaa ctttatctta atgtttaact tgttctgata gttattgatc tatagctttg 75780
atatggaggt ttgagaatga cctggaaaga attggccaca atgattgaag atagtgatac 75840
aagaataaaa gatgactgca aaatgtaaac ctgcaataac agaaagaatg aagtcactgg 75900
tctcatggga actgatatgg gagaaaaaaa cagatcaaaa ggctattcat gttttgggcc 75960
tctttgtcaa aatggaaatg agaaactggg gaataaaaat taaagcaatt ctagcatctg 76020
gttttaacat aattcttatc cctaaaaaga atctataaga aactcccaaa atgacaggca 76080
gccgtgggta gcattgcatt tcaagtaatc ttttaattgt taaaatttaa gtttccaaca 76140
tgaacataaa attttcaacc taaaagaaat gagttccaaa tctgagacaa gtgaaaaagg 76200
ataaagccta ctagggggta aattccatct ctttagagat ctagtaccca atttagcaat 76260
gtccaatcaa gcctttaact actacatttg aacacctcat catttcaaaa tgttacttaa 76320
tgatgccaat taactgtaca atgtctctgc atagcacata gccctaaaat gatttgtgca 76380
atgttactgt cagtaaaact gaactacagg gaatgctcat attctatgtc attatataca 76440
gaaatgcaat atcaataaag tgatatctgt tggtattaga aaaaagtgaa aattttcata 76500
tctttctatt ttcttttttc ctcaatggga tgctcttgtt aaagatagct ctgcatagta 76560
aggtttgtat aaacattatt tagctaaagt taaaaggggt aacatactgg ttctagcaca 76620
gatattaaaa caaattagtt tgtaggtagg gcagcaatca attatattac taaccatagc 76680
tttggtcctt ttatcctttc ccatttgatt ttacacagtg ggatgttaaa ggttgaatgt 76740
ctttggtatc tataaactta attgaaagct gttatttgtt tgtttaagtc tgttgatttt 76800
tataatcata attttactcc tatagatttc ttgtaggagt actatatgaa tttatgttgc 76860
actgaatttt gttatgttat acaaattaat aggcttttat ttatggaaag ctactattga 76920
tctgtcattt cttaaaaaat tactaaaaag tgttaaaact ttaaatgttg gagagtttat 76980
attttaaaag ttacatgcta gaaaaacatg atgtctgagt atattagaag ttatagataa 77040
ttcatctgtc aactataaaa ctctccaaca ctgcctttct ttaatgaata atatgaaatt 77100
tagcagtgaa aatgtgacaa tgtacaatcc taaataaatc aacaaattta gagatgtacc 77160
tctaaaacca ttgtaaattc aacagtgtaa ttttccattg gactttcact tattcattca 77220
ttaaacaaat gtttgtgagt gcctgcaatg tatgagacat tgtactgaag ctaggcagtg 77280
tgagttatca tatgggatta tcctttaaat acttctgagg gcaaaaaaaa aaaaaaaaag 77340
aagagaaaag gtgtgaggaa agataaaggg ttaattcatt aaaaaataac acttgaggac 77400
tgttttcttt gcaaggcata aagttatcac cctttcaaac agtagatatt tcacatttag 77460
gatgcgagac tccagttcca acaaagctca ttgcacagct gctaccctga ttaaactgct 77520
acatgaactc tgagcaatgt agcatggtag ccgcatgctt ctgcttgcat gatggttaat 77580
tccttccatt ctcattagtg attttctgag ctttgaaatt ctgatggtac ctaggatata 77640
aagcatattt atctaactga aaaacagata attagatgta acataaaata tgaatggctt 77700
tgtcacttta ttgtagcaga gaatgaatgt gggataaatt aaagctgatg ctagaacata 77760
tgcctatttt ttagctggaa aatttcaaga tttatgtact ttgggcttga gaaagaaatg 77820
gagtttattt tttatgcact gacatctctt tttttttttt tttggaagag ctctcttagg 77880
aatgaatggt atgtaaatac agtaggaatg taattataga ttttcctgac ccagttccta 77940
aataatagat atcatttcag aagtgcccca atacctgacc ttttgctcca agccatatca 78000
aagcacacat ctagtctact tttcactctc attcctagcc actatgacaa tactattcag 78060
ataaaacttc tagtcctcta cttatgtgac tcataccaac ttgaccttac gatagtgact 78120
gggggtgcat atctaggttc atgctgtttg tccattatta tggttttgtg agaaaaggca 78180
aaatttctag gtaaagtgtt atgaggacga ataatccacc aggcaaccaa ctgacccttt 78240
catttgccat cttgtcactt caaacagctc tccagaacct gcagccagca cagaccaaag 78300
tcaggtttgt ctcctcttct gttgatgaac aaaggttgat tccatatcgt ggctattgtg 78360
aatagtggca gtaaacatgg cagtattgta tgaaaatatc acagatagcc cttaaatatg 78420
tgcaactatg atgatctatc aaaattaaaa attaaaattt atttttaaaa gttcagttag 78480
aaagcttgta gttcctggca aactactacc tttctcggca aaagaatttg atatctctta 78540
aatattttct gcctaatgct gatagattgt atttacatat tccattaatg caataaataa 78600
aattacacca aaacatcagc attatttatt tccaggggca tctctcaaaa taaattcctc 78660
caaaattcac aaaaccaaaa ccaatgtgaa attgtactca gggatgcaaa tgtagcccag 78720
tgaagcattt gcccacttgt ttggtattat tgaagcacaa ttagaaaaat gtgcaatgta 78780
tgcccaaaaa ttctataata agggccaggc gcggtggctc acacctgtaa tctcagcatt 78840
ttgggaggcc aaggtgggca aatcatgagg tcaggagatc gagaccatcc tagctaacac 78900
catgaaaccc agtctttact aaaaatacaa aaaattggcc cagacgtggt ggcgggatcc 78960
tgtagtccca gctactcggg aggctgaggc aggagaatgg catgaaccca ggaggcagag 79020
tttgcactga gcctactctc cagcctgaac gacagagcga gaccccatct caaaaaaaaa 79080
aaccataata agaacttttt aatatactat attataatgt aaaaagacta gatgtcaaac 79140
aaattaggtg atgggaagga attgagggag aattttagac taagcaattg agcagcacct 79200
gtttttcacc acaaatctgt tacatgtatt gctcaattgt gctgaatcca tattgggtcc 79260
tggtggctat gtaatagtct ctttcttgga taaatgtttg tcctctctta tggtttacta 79320
atggtgtaca gaacagcatt gaatagtggt tatttcctat gacttcctag atatctctct 79380
cataatcctg aatgttttaa agatcattct tagatagagt acagctagac acgaaccata 79440
gtggaaatca ggtagacaaa atttaaaagg agtcttaatt gaaggtcatt ttattgtcct 79500
cagtattaat cttacttaaa acaaacctgt cactgagcag aactcaaaac accagagccc 79560
tttgccaaat gtgatttttt acaacaggag cgctggcagt tgagaggagt attctgtcac 79620
acttgagaga attcgagtcc ctgaagattt atatgaatgc ttagctatta tcgaaccatc 79680
tcttcacaga tgacttagta aatgtctgcc tttgcatcag ataatggctt acaagttaat 79740
ctcctcttgc tccctgttac acacatatac accttcttcc taaacagctc ataaggtgaa 79800
agaaagactc agatttctga ctatgtaatt gataatatca cacggactgc ctgctcatca 79860
tctgctagtc acattggcag agttgacagt tttggagaca ctgaagacag tgcatatatt 79920
aggaaataag cagtttcctg atataaattt tcttgtagtt tataaattac atagcattta 79980
ttattccctc atattttata acatttaata atagaactga cacatatatt cattttaaac 80040
tcaattgtgt ataataacta tcatagcaac ccttcagtgc ctaaatatca aatcttccat 80100
tcctcccatg aacatcttga atatataggt actgtggtta gctccaacaa gcttttggtt 80160
agaattcatt gcactgatac atagacattg ttttaaaggc aatttcaaat caaagctgtc 80220
agctgtgaat caagcacacc ttaaaaagtg acacatttgt cactagattc cagcctctca 80280
aattactgac acgcatcctt tttatgtaaa gatgacattg ttctttcctg atatattgca 80340
ttcctcatga atttcttata gtcatagaat ttttataaac catttcagaa tcgctgaaat 80400
aaacatcaat atttttaact ttttcattct gtcaaaaata ttgtatgcag agatattgct 80460
gtaagtgtgt atacctgtgc ttaagagact agggctgaag agaagtaatc aaccgaacca 80520
ctggtgtaaa tgtgcgtcac atttttagtg actagaaatt gaaataattc caacaaattt 80580
atgtgctttg ggcttgagaa ttcagactgc cttaggctaa gataaaaatc ttttcctggt 80640
actatatacc ttcttttatt gaatgactac ctggctcttt ctattatata tgcagatttt 80700
gtacctctgg tcatctttgt aaatggtgcc taaaagatat ttgaagaata agtgaccagc 80760
aataagaaca aatgtctata caaaagcacc ctttagttgg atgtaattca ctactttgag 80820
ttgttaataa cctctaagga tgacagtagc tattagttga ataaaccatt atgtctatta 80880
ttagaacact agatagttta taagtccaaa caatgcataa aatacctatc tcatgttacc 80940
attgtttagg ttaccagata attgttctgt ccaattattc cacttaattt tttgcttgcc 81000
cattagctaa atggcaagat aaaatttgtc aaacgggggg gaatgtattg aaaatgctag 81060
acaactacac ttaaaatgaa aacaggccag gcgcggtggc tcaggcctgt aatcccagca 81120
ctttgggagg ccaaggcggg tggatcacct gaggtcggga gttcaagacc agcttgacca 81180
acatggagaa actccatctc tactaaaaat acaaaattag ccgggcatgg tggcacatac 81240
ctgtaatccc aactactggg gaggctgagg cagaagaatc gtttgaaccc aggaggcggt 81300
ggttgcagtg agccgagatt gtgccactgt attctagcct aggcaacatg agcgaaactc 81360
catctcaaaa aaaaaaaaaa aaagaaagaa aagaaaacaa atgcataatt tgcaaatatt 81420
atttttatat tgtatgttat ctagggcttc taaatgcatt cttcttataa gcctaggttt 81480
gcaataacat tcatttagaa ttgagtaatt ttaaatataa tattttataa aataaaatat 81540
aataatttct cttaattctt tgaaaatatt aaattaaaag ggggttgcaa actctgcatt 81600
ccacatttcc atcccaacat ttaattttag caattttgta gtctgcctaa aatgcaatcc 81660
atcatttact gtttagaaaa tagggaatgt acacaaaggc ctttcagctt tccctgaact 81720
ccataaaaat ctttttgctt ctttactgcc cccctttgtc aggagttctg aggaactgtt 81780
ttttatctta agtctcacaa agcatttagg agaatattta aacttaaatt cttttaaaac 81840
ttatgttcag gacaaagtaa cattgtatgc attggtgtca tatgtattta aattttgaaa 81900
tttttaatac tggcaaaatg aggtttcaat tttaatataa attatttaac aatcttaaat 81960
cattaaatat attacttaat atatttaata tatctaaaca gtcacaattt tcccatacta 82020
ataatcataa aaaatcttac ccaatggtca tatagatata cttaatggag ttttgggggg 82080
gtatttttgt atattaaaaa attcatatat ttgccttact tagaagaact gattaaatga 82140
aagtataata ttaacaaaca tattgttatt ttatatttgc atttgtgata attatatttg 82200
aaacgttcaa gattttccaa tgaatttctt ttgcatttgc gtatttgtgc ctttttatta 82260
taaaaatagg tggcttttta gttccactgc ataagtttca acataggtct acaaatagtg 82320
catctttttg aagttaatca ttataatcac aaattgaagt tgcctgagct ccaattggag 82380
tctaaatgga tgactgaatc ttattattcg aaacccactg ttgctacaca atatggccac 82440
acaagagagt acacaagacc cgtctgattc agcctcagtg ccataaatat tttaatggtt 82500
tcgttggaat ctggaaatgg agctcaccac aggagatgct tcttcctttg actctcatta 82560
ttatttcctt tacaaattaa ttaataaaaa cttagatgct aaattagcac ttgatgaaaa 82620
cttatatagc cttgacattt tgattctgtg agtgaataaa aatacttgga gaaataaaaa 82680
tcctaatcat gttcaggaat acccacaagg taacaagtac atttttaaac tttaaaaaca 82740
tttattattc atgataaaac atgttgtgtg atttaaatat aaatttttat tatttgcttt 82800
aacttatttc cggattaaaa agtaaatgtt tacctagctg ttctaaatgg taatcctcat 82860
gattaaaaca gcaatttgtc atatttcagt tacaaatgat cttttattat tagttataga 82920
acataagttt cttcattgac tgaggcgatg tttcaagtag ataaatctgt taaaaaaatt 82980
gtggtcatat tctgttaaat tctcatacca ggcaatttgt ttgatattca ggaaaaacct 83040
agccactgac caaaaactct acctgccttc tcagttgtat cctcttggac ttaaagggga 83100
ctgggaaagt tataagatgg ttcatgatag tccatcaaca tcccaagaac aaaaacagat 83160
gttgtactga cagcatcata tgatcatatg catgtaagag cacattcata ttgccaaatc 83220
agttggaatt tttcacggtt gaaagttaaa tgaaatgctt agatgtatga gtcatcggag 83280
ttaaagacaa ttacagccag atttatggct gtgctaaaat aaagctagtt agaaaacaga 83340
ccaaattcca tgacgatacc aagtctgact aatgattcac cttaaatttc ggagcaacat 83400
ttatcctcac ttgtttgttt atttgacaat gtgcccttat ccattaagta actaggagga 83460
agggaaaagc actacgtggg tgagtgacaa gacactgaca ctgatttgtg actttggata 83520
attcctggat gctgttatct gttttggcat agagatggat ctgtaactgc taataattgc 83580
cgactgtgac catcccagag gccatttact taacccaggt atttcagacc tgacagcccg 83640
aggataaaca cgatttccct ccatcactaa cttcatctgc agggcctaag cctccttcac 83700
agtctctcca gtgatttatt ggcatctcca agggtatctc acatgtgctg aagaacaaat 83760
ctgctcactt tcatctgctt ggttttccct tttgaaatct gctgctttaa aattactaag 83820
ggaggaatca tgcctgctgc tacccttgcc agtgaccttg cagtttgtgc cctgattgtt 83880
ccaattacca caatcaaaac agaagcgttt gcagttactg cagtgctctc tctgtggatg 83940
tcaggtctga ctcagagagc caggctgggg aacagccatt tccactcttg tacctctgca 84000
aaaggacttc catgttccgt aaacagactc ccacctctca ttttcccccc aagcaaagca 84060
tcataaatta gagagcatgt aacgggaaag aaaatccatt agccatttgg gttcagtcag 84120
acaagccagc tcatggaaag tttatacagg aaggtcacat ttcaattgag atcaggaggg 84180
tgaaagggtc cagctgtgtg atgagagaga gaatgttcgg gaatgtggaa cagaggtatc 84240
caaggcagaa caaactcgta tatgaaggct ttaagggtgt gcaaatctag catattttat 84300
gacataaaag agtcctgatt agctagaata tgatgaatgt gagaagaggt gaaggctgga 84360
gataggaaaa attattccag atcttataag ctatagtaag aaatttgcat attatatata 84420
gacttgtggg aagccattgg attttgtaag aaggagatta acattatctt atttatgtta 84480
tttgtgattt ataaccccaa atgtgccaga tacaaacaaa ccaaaaataa taataataat 84540
aataagaaga agaacaacaa cagcaatgga actgtggtga tggttttggt cacaaaatgc 84600
atatatatct atttttcaca atgcaaaaat atttcattat ttcaaatttt aacataaatg 84660
tgggtatgca tgagcttaca aatcttgaag tttattgggg aatattggtg agcatggttt 84720
ttattgcatg gtcacaactt actaatggga aacatctgaa tacctattga gttaatgcat 84780
gcacattttt attttcctgg aatactgaga aaaaggttgc tacataatgt cttgatagct 84840
tctaagtcat ggctcaaaag tgaatgtgga atctgctaat cggaatggac tcagattcag 84900
ccaagttctc aaaaacattt gctttcatag atgtcttcaa gaaacaagga gtcttgaatt 84960
taaattgtga agtgtctatc ttagaataga gagatttaaa atctgactgt attttgttta 85020
aaaaagccta tataactgta ttatataaaa ttatttatac tacagttaaa aaaagaatcc 85080
catcctattt gtgcctaaat aagtgcctgc ttgtagcatg aaaactattt gttgagggtc 85140
cttagatcct cagagcatgc tgtgaaagta ggtacaattg ttctttctat ataagcctct 85200
taagataaca gataattgcc agaaatacag cacacagtac aaaattacct tgttttactt 85260
ttgccacaaa aaacaatttc ttttggcttt gagcaataaa gtccaatgat ttttttcctt 85320
tcaaaatatc ttcctccctc tccataagtt ttatatttat tcacgaagga atattccaat 85380
atcggatgtt tttgtctgtg tctcttcctg gaacaaatgt taattaatct ctttgggttt 85440
gtatgtcaag tggaggggtg gggattgggg acaggtgata gttgtctagg gagttaactt 85500
catctctata ggagagtgga tagacgctgt atacgaaaag ctcttgaaaa gggaaataca 85560
gcagccactt cctcagggct tccatggtgg tcagactcct tgattgcttt agattaactc 85620
tggcttttgt ccttcggagg ccaccagatt gggtggatag acattgtcct tgctgttctt 85680
ttgacctacc tacttgtact ttaggggaaa aaaatgcctg taataggtta aatgctttct 85740
caaagatcac caaagtatat aacacatggc aaatagacag agaaatgaga cagtataatc 85800
agtataattt ataaaagtac cttacagcag gatcccatgg gatatgggtt ttttttaaaa 85860
aaaatctacc taatcttttc attgaactcc tattcaggat tcattatatt gaatatggct 85920
cagagacctg gaaaattgtt tccacctttt taatttattc accatcattt atggaagttt 85980
tcaaggacgt ttacttacct acctcagtta acagattgta ctacttggga agtctataaa 86040
tatgagctta aagcattttc tgagttttaa aataatttag attgtgtaga atgttaaaac 86100
taaaagagga aaaaattatt cagttcctca gttgaaccta gcaatttatc ttttcacagt 86160
gtgctcaagt atagtttttg aaaagtaaag aagatggttt ttatacaaac ataaacacat 86220
ttcaaagatt ttattcaact aattaattag tagtggagcc aataagctgg taagactggt 86280
ttaaaggaat atctgaggaa taaagattta tagaaacagt caaagaaatt ctaaagagaa 86340
ttgactaata gatataaatc tagtaaatat ttgattaata atagcagtaa cctatggaat 86400
tatgttttct actgagcata aatgagcatg aatctctttg ggtttgtatg tcaagtggaa 86460
gggtggggat tggggacaag tgatagttgt caagggagtt aacttcatct ctataggaga 86520
gtggatagat gctgtataag aaaagctctt gaaaagggaa ataaagcagc cactgcacat 86580
ctgcacatat aacctgtaga tctgggggct ctaataaaaa agttaatggc aatgtcaaaa 86640
tctggtgttt tatcttagat aacttcatag tcattgattg agccccttaa aaataacatt 86700
taaaggacat gtagtcattc tgtttcttta ttgccaagtt ttcagcaatt tttctcatga 86760
gaatgagtgc taagaaactt ttggtggagc gtggtggctc aagcctgcag tcttgcactt 86820
tgggacgcca aggctggcca attacttgag atcagtagtt tgagaccacc ctggccaaca 86880
tggtgaaacc ttgtctctac taaaaataca aaaaaaaaaa aaagtgggat gtggtggcat 86940
gcgcctgtaa tcctggctac tctggaggct gaggcacgag agtcacttga acccgggagg 87000
cagaggttgc agtgagccga gatcctgcca ctgcactcca gcctgggcta cagagggaga 87060
ctccatctca aacaaacaaa caaacaaaaa agaaactttt aaaatataac aatagagaca 87120
ttacataggc ccacaaaacc acctccaaaa aagcattcta tcacctgcaa gaaagcatat 87180
atatatatct gcttttgtgt atatatatat atatatatat atctgctttt gtgtatatat 87240
atatacacac acacacacac atatgtgtga tatcagcatg tgtatttaca catatatttt 87300
gtgcatgtat atttttaact aaaaatgtgc taggagttag atatgaactg attttggagg 87360
aggtgatatg ctgtagagag agagaatggg agaatagcag tattataatc tctctccatt 87420
gtattcagtt tttttctttg tctgaatttt taatagaagt cagccagaag atgttagttt 87480
ctgggaaatg tgttgagatt tacagtcaaa tccagagaga actagaggct tatgagtaaa 87540
taagtaaagg ttatgcagag aaagtattct ttttcctgtg taaacttgaa tattggccag 87600
gcgcggtgga cacctgtaat ccagcacttt gggaggccaa ggcgggtgga tcgactgagg 87660
tcaggagttc atgaccagcc tgtccaacat ggtgaaaccc attctctacc aaaaatacaa 87720
aaattagtgg gtgtggtggc aggatcctgt aatcccagct actacggagg ctgaggcagg 87780
agaattgctt taacctagga ggcggaggtt gcagtgagct gagacagcgc cattgcacta 87840
tagctacggc gataagagtg agacttcatc taaaaaaaaa aaagaaaaga aaaccttgaa 87900
tatttcttgt acttgtgttc aaatcataca gttatgaaag tttaccccta gctgttacac 87960
ttaaaatgta cttctgaaat atacagagag atgatacaga ctattaatga gttccactaa 88020
acttttaatg gtttagaaaa tacaaatatt ttcttatttt tctggaattc cagccattaa 88080
tgtaaaacat tggtttcaac ataaataaca cactggcatg cacatatgcc taagcatggg 88140
cccccacaca tacagacatt ctgaaagacc actttttaaa aatattcagt accgtatatt 88200
gtgcattcct tctttatcca catacttaag ctgctgcaag catcccattg ataacaccag 88260
taataaaaga tgggaccatc agtaatgaga tttgaaagcc ccttttgcaa gaaagtaagg 88320
actagaaggt ggaaatcact ctgtcttaga gtcatatgga ttggggcttt gctagaagtg 88380
tgtgctctca gggaaagctg cctttttatt ttctccagag aaaagccttt ttgtcagtaa 88440
aagaagatgt atcatccaat gcatatgtaa aattctaaac agcagataaa acaacattca 88500
ctattaatct ctgcaaaaga agatatattg aaaaaatcct caagtgtccc tctttgggtt 88560
tctttgttat atattaaagc agttatcttt agatgcatga gaatcacctg aagaccttat 88620
ttttaaaatt cagattcctg tcagttcact cccaaagatt ccgattcagt agttaagaga 88680
caaagcctag gaatgtgaat ttacaatcaa cacctcaggt gatagccatg catgttctta 88740
atgctctact actatctatg cataaaagga agataaagtt ttaaaaactt gaaatgtggt 88800
ataacagttt agtattgaat aatatacatt tttacttatt gtaacaaatt atgatatcta 88860
cttggggcaa cagtatcttt tattttggat ctgaatccta attttggcta ggtatcactg 88920
agggattctt agtctaaaac aattaaatgg agttagtggt tttttttagt aactcttgat 88980
tttctgtttt tttccattgg catcttacaa aatttattca ttcatttttc cctttttcac 89040
ttggcattat ttgttagaca gtggacaaaa gaactataga aagtagagaa gcatgtgatg 89100
ttgtcctgct cttagattct cgcaactcag gagaggacat tcgcttacac caatcatctc 89160
aaaacatggc agtttatgct gaactcagtc caatgggaga gcatttgact gagcacatag 89220
ggagagaagt tagctctgtt gaaggataat caacgaagaa ttcttaggaa aggtacagtc 89280
attcattgaa tatttgctcg gcacttacta ggtgcatatg tgcactaaga tctaaggatg 89340
ggctgatgaa gaacccaggt cccttttctt ctagtggaca tgcagactgg cctaaaaaaa 89400
aaaaggtaac tggaaaatgg ataaggaaac tgagtcactc ggtttattta ttatcactcg 89460
gtttatttgc ttttgtttgt attttcattt tgacacagca cagtgtcatc ttaacgcatc 89520
ctccaaagtg aaggatgggg tggataacac tttagttggc atttctgtag ccaggagcca 89580
ggatctttct cccataattg cattaacctg ggaaggcacc ctctaggtag atttgtatag 89640
caccctggtt aatcaattat cagtttactt cttgtctcac taagctttaa caccttacat 89700
ttatgaagca gtgtaaatat aactttagca tcttgatcac agcaagcacc tgatttgtat 89760
ttttttatta gctcaagtga aatcagatca gagaagtaca ttacaggtca taaaatatgt 89820
gcaaatttca taatgacctc cttttaaaat gtgcaaaaat aagattgtta aggcacattc 89880
cagagccttg gggggtgtgt gtgtgtgtgt gtgtgtgtgt gtgtgcgtgt gtgtgtgtgc 89940
ttgtcttttg agaatatctg tatatcagaa aatttggctg agaagcaatc ttcttcttag 90000
tggttctttt tctcttttga aaataaagta ctaaaaatac ttaaagatgc agaacagcaa 90060
cctgttccca gtgagactct cgtttaatta atgtggtgat ctatatagag aaaagggaca 90120
attgcaaaag tccctcaata attatctaac cacagtcttt aggtaattac agcagaaaga 90180
ttttcaagac acaaaacacc ctggaaaatt tgacctctta ttttgattca ggcctttcat 90240
ttcttaaata ttttctttaa tgttgatgtt tatgcttgac aaggtcagcc taatgccaga 90300
tgaatccctg gaactcaaaa cattgctgaa ttcacagttg aaggatttta atataatata 90360
ccagctttta aaaatcctac agtgagaata acaggactga ataaaaaaat taagaaatgc 90420
tcaggtagaa ataaatagag aaatttagaa aaaaaataaa acgtattcaa aataagtatt 90480
aagcattggc aaagaaaaaa tagtagcaga caattacatg ttccatttgt aaagatgatt 90540
attaattagt ggtcttgcaa aacattggag aaaatttgct gaaccatcac attcataaat 90600
attaaaacca cccattagtg aaaatctttt tactaaactt cacaactgat agtcaaataa 90660
tgttcagttt ttctccattg caataaaaaa taaaggcttt tgccttcaga tcagtctctg 90720
ggccttatta attcagtcag ccagaagcca catggaaata ttttgttttg ttaaaagcca 90780
gcttgccctc atgatctttt aaaatctttt aaaaatcttc catcagccct ctccctgact 90840
tgaattatgg cagtgctttc taaactggta aactcaatct ccttggtgtg cctcaagata 90900
gagtacataa accctcctta gaaattgagc tctcaattct aaattgcact ctccatgaga 90960
gcaagcaaga atgctttgct ttgtattaag tggtcacaat attaaatata accatagaca 91020
gcactgtatt ttctaaacac cttattttct tttaatgact gacataaatt agatcataag 91080
tatacaaatg catatctgtt gtatttttca gcaccatgtg tttttttttc ttttttctga 91140
gttattttcc tgctttcggc agccttttct ctcaggtgcc ttgtgatcca cagtggtgtg 91200
tgttcacact aaccaaagca atagtcttac ctgccagaaa tagctgtgac atttaaagag 91260
aggtccaggg gaaggcacag tgcttaacat ccaagtctga agagctaata gtgaaattgg 91320
ggcatcagct acagagagat ttaggggaag taacaggcag gttaaatatt ttatggaaat 91380
gatttctgtt ctgtatatga ttgcaattaa cacatgtcaa tctgtttcat taatttgtta 91440
actcatctat tatgctatgc catgaagaaa ataaaattgg agttctttat ttttttgaga 91500
tggagtctca ctctcttgcc caggctggag tgcagtggca ggatctcagc tcactgcaat 91560
ctccaccacc caggttcaag cgattcttct gcctcagcca cctgagtaac tgggactaca 91620
ggtgcgtgca accatgcctg gctaattttt gtatttttag tagagatggg gtttcaccat 91680
gtgggccagg ctggtcccaa actcctgacc tcaagtgatc cgcctgtctt ggcctcccaa 91740
ggtgctggga ttacaggcgt gagccaccgc gccccgccac aaaactgaag ttctaagctt 91800
cagtttagat gctcactaaa tgcttgtttt gcaatacctg actgtaactg gcaggaatat 91860
gttttgaaag tcctcatttt ccaggtatgc agatgaaata taggggcatt atctactatg 91920
tcaaattata atgatttatc agtggcacat gaaagtcgcc tcacatttct taatcagtga 91980
tataccatta tgtcatgcca ccttttaatg taatatgttt acatctttct ttagatgtaa 92040
gcattcattt agttcatcac ggtggctttc acacttactc caagaacgct atgagttcct 92100
ttgatgtgct caagtctcct gccccaggga gaaagggagt ggtgagcagg aatcgcttta 92160
atctatttac acagatattt tcttttccat ttattttaaa ggaatttttt ttaacttaat 92220
gagtatgcag tgacggtggt gatgatgatg atactaaggt ttaaatgatt agatagtcaa 92280
atctgggctg gaattgtaat actgttttga cttttaatct tagagaagct ccagtctgct 92340
tattttctgg gcataaacac atgagaacaa taacacagtt ctgttatctg aatgttgtta 92400
tattttgttt gaaacattca gtgactttca aatattgtat ttgcctaaga aaattcaaca 92460
gagtcagaca ttctcttcca ggttaaattt ggtgagtctg ctaggaaaat aaattttgtg 92520
cactggtcat tctgatctag tggacgttct aataaaagca cctttgtgct gcctacgtct 92580
tcactttaaa gataagatac ctgggtactc gacaccaaat tatagtttga gatctcaaaa 92640
atgggatagg gaaaccacag ctcaaaaaca aaaatactag cactggaaaa gatagaacta 92700
gtgaagatga atcattctct agactttaaa ttcagagata tcaaaattaa gaaaaagtag 92760
gaggaataaa aaaagagggt aagcaaaaca atataagttt gtatagcaag agggtataaa 92820
gcaaatacaa tatttttcag aaaaattaaa taaaaataga tttacataac attgttttta 92880
atctcaaaga tcaaatttca attttcatct cattttaaaa cccatatgca cagtctcctt 92940
tatatacatc agttgggtgt caaagtgact tttttcttgt ttccaaatac agttattttt 93000
aaaatttaat tgtatgattt aggaatttga aagcaagcca gtttgcacac acatatgtta 93060
ttatatgtgt gctttagact tggtttttag ttaatgtaac atgacagggc cacctgagtt 93120
atttgtttac aaactagctg gaaagccacc ctggaggaga aacctggcaa caaaatggtc 93180
tgcagctttg ttattgttat ctataggatt ggatgccatt attgctgtaa aatagttcac 93240
aagaactcag tctatgggaa agactcaaaa attctttgcc tgttaaagaa aaatcaggat 93300
attggactgg ttagtttaac taaaaagtga tgatactcag attctgcttg gattcactgc 93360
ttctcagcag ttgttttgtt tctttctaat tgatatttta tttttcagag aacccattat 93420
aaaactcttc ttcttccctt aaaatcacaa ccacacaaca gcaattaaaa catgctttga 93480
cgtaagactg atatggtttt aaacccagct tgactatcga attttttact ttaggcaaaa 93540
cacctctgac atttatgtct tatcgtcagt aaaaaggggt gattaacagt tttacaagat 93600
tattcaataa ataaatataa attcctcctt ttccttcctt tcctttcttc atcttcagca 93660
tctgcatgcc ataagctcat tttagttctc tggactcatg ttaacatgtc ccacctttcc 93720
caaattaaac atcatctctg ttattggctc cattcttttc ctctcatttg agacaattct 93780
ttatcaacca acaccctctc tgctctgtat tgtgaaactc tgctcctact acattaacag 93840
tctcttggtt tctttaaaaa gaagacaaaa caattaaaga acagaagcaa aaaatctact 93900
caaatcccca attgttaccc tcaaaattaa ttgtcccacc cctagctttc tcattgcaca 93960
actctttgtc aaaatgtttt ctaccatcac agccttcaat gatctttctg gttcctttat 94020
ctcctgaagt ctgacttcta cctccatctt tttctggact attcaacaca ctttgagaaa 94080
aaacatactt ttgttaaaca ggtatgcatc cctgaagcat aaaatacata gtactgaaag 94140
tgcacatgtg tggttcttcc catttttttt acagcacttg aaactgacaa gtagtagtac 94200
caattactta gtaaaagacc tttttcattt catttctgaa atattgttat tttccttttt 94260
catcttccat ctctgactac acctccaatt ttacctcttt gctgccttcc ttcctaagaa 94320
agttcttcat gcaatgccat cttgtttttc ttcacttgcc tctttttctc actttaattt 94380
tatgaactct gatgacttac ctctgtagtg taactactca aaatatgtat ttctgaagtc 94440
tcaactccaa tctcatattt tcaacttata tttatggagg catctcagac tcaacctacc 94500
taaaaaatgg cttatctgcc ctaaaatcta ctttgttctt tttttctcta ctgctaataa 94560
ttatcttcct agttggtcaa gctcaaaacc taatcatttt tactccttgt ccctgtgtca 94620
gctgtccaca ttcaagcagc gtatcatttc tgcacatttt tcaagcaagt cagtaactgc 94680
cttttgtttg ggactgtctt ttcatatagt gaacagcctt ggaagataga aatcatttct 94740
ccttctaaaa caaaaggcag gtgtgcttgc agccttggat agaggtagtg cctctttcta 94800
aagcaaaggg acatctttac tggccattat aaaatatcca tgtttcctga gctctgcgtt 94860
cctcttttct aatgcaaccc actgagcatg taggtgtcac ctgagctttt ctgtgggaat 94920
tgcggcttga ggaatcagtg caagaaaatc atgatactct tgctaatgct attaatgtga 94980
gtagtaaagt taattgtctc tgacccagca ctattgtgtc tttgcccagc actcaaaaga 95040
ctggcaggct tgcaagtagg acaaaatgtt agatttttca cagttcttct gcttataagt 95100
acttgttaaa accaattaaa acacaacttg tagtttgcac ctataatttt gtagcatttg 95160
cttcttatct atgtcactag gatgtgctta gtgacagacc catctatcat ctattactca 95220
agtttttggc tgtattccta ggcaacagag agaaggggaa caaacaagag gacctgtgca 95280
cagtttgaga aaggcaaaac accgagctta attgcagact tgaatgtagc tagcaaacga 95340
agtaaggcaa aaggttcctt tttttttttt ttagatggag tctcactctg tcgccagtct 95400
ggagtgcagt ggtgctgtct cggctcactg caacctccgc ctcctgggtt ccagcgattc 95460
ttctgcctca gcctcccgag tagctgggac tacaggcatg tgccaccatg cccagctaac 95520
ttttgtattt ttagtagaga cggagtttca ccacgttggc caggatggtc tcaatctctt 95580
gaccttgtga tccgcccatt cggcctccca aagtgctgag attataggtg tgagcctccg 95640
ttcccggcca aaagtttcca ttttttaaat agttgggttt ttagtttcga ttctttccaa 95700
aaaaaggttt tcttaaaaaa ataaaattag caataagatg aaatataaca acaatataat 95760
cttattaaga caatatatga tatacattta tcaaaatact tatattttca aaagtgctta 95820
aaataatcta gcacatagta gatgctcagt aaatatttga tattatgact gtgcatgggt 95880
cattataggc tactttatgt atatcatttc atttagtaca acatcactct gaaaaatgtt 95940
ttattgttac cgtttttcag ttgaaacatt tacgttgctc aagatctcac tggtaccatc 96000
tactattagg tcagtctgcc accaaatctc atgctcttaa atgccctttt tctcctgagc 96060
ttccaacaaa tagtgtactg tatataattg ttgaagggag gggactgtga gacaaaatat 96120
ttagagtgaa tgtgtagcca caatttcagt tcctcaacaa agtgataaaa ttaggaatca 96180
tcctcaatat atattcttcc aacacacaca cacacataca cacacacaca cacacaaata 96240
ccacaagccc acttgaatgc accccaccta cacattgcaa ccatagagac aattgcagca 96300
ttaaatacag aatattctgt gtgttgtttg tttgttctcc ctttgctaca aaaatcagaa 96360
tttctactca ataaacagca aagggagata caaatgaacc aaattaaaga aggaaaaaat 96420
gttgaaaaaa ttatatacag aactatgtat tgatttattg agagttcagt aatgtaatcc 96480
agaaataatg gatgccttaa aagtaattaa aagaatgcaa ataaacattt agtgccaatt 96540
aaagaaaaag aaatacaaca ttagacaaaa taaaagatat tcatttgatg caatgaggaa 96600
ataatctttt attcctcttt aaattctctg tggaataagg catggttata aataaataaa 96660
catctgcccc atggacttaa tggatcgtta tattttattg cgataatcat aatgaaattg 96720
ttgggaggga ttagtatctc tagtgtaatg ctaagaaaga taaagcctgt gcccaggcaa 96780
aagctttctt ggttggtcaa aaggtttgaa gacatttcaa actattctaa aacaaacaaa 96840
caagcaaaca aacaaaaaac atacaatgtc tttgccacat atttaggaaa caaaatgaac 96900
aatttatttc tgacaacctc atagtctttg ttctgtcaga acaataatgg aaaggtctaa 96960
accagaaaat gctatgcatt gaatttataa taaactattt tttcctgtaa caaaaaattg 97020
ataaacttga tatttgcaga tttaatgatt atgtgtttaa aaaaaatctg gtttttgccc 97080
ttgcaaaaaa tcatatatat acacatagat atgtatgtgt gtgtgtgcat agtatatata 97140
tatgtatata catatatata cacacattta tatatataaa catttccttt aacctcctat 97200
tttattccaa taaaaatatt ggtattagag atagttctga tatttcatca tgaatagtta 97260
acattgcatt tggaaaggat taattttttt gaaacgtaat tttaccttaa taagtagccc 97320
agcgtaatat tttagtaatt acacagattt ttttttcaag acatttgaca actaatattg 97380
cataatagtt aagagtgtgg gctttggagc cagacttcct atctctgttc attcactgat 97440
aaaatggaga cagtagtaac ttcctcaaag agttgttttt taagatcaaa taatgcatat 97500
aaaactcttg aaatggtacc aaatacagag taagcaccaa ataaacatta actgttattg 97560
ttattccatg tccgaataac acagaaaagt aagaatttta atatttcatt tgaatgacct 97620
tttaaggata cacctagccc attatctttc ttgataatct tgtaagatga ttcctttttt 97680
atctccgatc tgttgaggca tggatagagg ttttcagaga aaacattttc taggtaactg 97740
aaagaaagta gcaacaacaa actgtgacaa aacttaacaa tgagagaatt tacaagatag 97800
aataattgca actccttttg aaatcaacca ctatggtcct ctggctggga tagctaagca 97860
aagatattcc agcctgaagg ttgagatcta cttgaagagt tttctatcca gattgtgagg 97920
gcccctcaaa cttcacttag tatctgtttc tattagtatg gaaacttctg gaaccttgtg 97980
gtatcacatt cacttgacta ctttattcct gctctagcta tcttaaagcc tttcttaatc 98040
ttttatcttt tagagaagat acttctaggt tttaaatcca ccgatcttga agctattgcc 98100
ttcactctct gcttcagagc ccatcctttt gtatatgagt agtttgtttt gcctaaagta 98160
ctttctccca gtcagatttt aagtccagtt tctcatctgt ttttgagagc aaactcctgg 98220
gccttggctc actaacatct tgacagcata tttcttcttt cctatgggct tttcagcatt 98280
ccctgggttt ttctaaaata tgaaagcaga ctctttatct cttactttgt caaagcctac 98340
cctccccact gatttctcac ccagttgcta gttttaagac ctgcctctgg ccgggcgcag 98400
tggctcacgc ctgtaatccc agcactttgg gaggccaagg taggtggatc acgaggtcag 98460
gagatcgaga ccatcctggc taacacagtg aaaccctgtc tctactaaaa ttacaaaaaa 98520
attagccagg cgtggtggtg agcgcctgta gtcccagcta ctcgggaggc tgaagcagga 98580
gaatggcgtg atcccgtgag gcagagcttg cagtgagctg agatcgcgcc actgcactcc 98640
agcctgggcg acagagcgag actctgtctc aaaaaaaaaa aaaaaaaaaa aaaaaaaaaa 98700
agacctgcct ccaaatatca ttgtatttgc aaacatgaaa tgacttattg attctgagct 98760
cagcacaaga gcaaaccttt ctcagcttga cccatcttca catcgttaat gtcttattca 98820
gtcactaccc aaggggctga ccttcaagat tctaatccat gaaagcttaa aatagtaaac 98880
aaatttgaat atagtttaac atacataata aattttattt ctagaagagg aggatcagcc 98940
cttagacatg aaaagtaaaa atagtttatt cccagatttc cctttgtgca ttagtatatt 99000
caaccgagtc tatccaagta acaggacaaa aaaagctggc agttgttgct gcgctgtgaa 99060
gtcttattag gtgagtcagc taattatatg gcactaccat aaatacagca ggcactgccc 99120
tgcttgttag gcttgccaag gaaaataagg atttaaagca gcatactacc tctttgctat 99180
ataatgacat tttcttctta aaaatgattt tgcaccaatt cctgatttat ccaccaatta 99240
ttttttaatt tatggttgaa tgtatttaaa cctgaattca gagataaaac tagtaaatag 99300
ctccccaaaa taaccccaaa tatatttaat atattagctt tactctctcc tccactgcca 99360
aacctttaaa aactgaaata aattgttttt atttcatctt ttctcttttt ctctctctct 99420
aaggtgattg ccaagactaa agaaacagct agaagggcaa aagacaagaa aatcagtaag 99480
atagtaacag attatccaaa gtagagcacg gctcaggtgc agtggctcat gcctgtaatc 99540
ccagcacttt cggaggctga cgcaggagga tcacttgagt ccaggagttt gagaccagcc 99600
tgggcaacat aatgaaactt catctctata aaaaaaaaaa atttaaatag ccgagcatgg 99660
tggtgtaagc ctatagtccc agctatttgg gaggctgagg ctggaggatc acttgggccc 99720
aggagttgga gactacagtg agctatgatt gtatcactgc attacagcct gggcaatagg 99780
gcaagaccct gcctctaaac aaaagataaa caaagtagag cataaatggc ttctaaatat 99840
atgttattta tgtgtaagac tgggttctct aaaggtatca tttaattaaa atagatttgc 99900
attctcaatc tgtaggtatg gattatgtat aatgtattta agatatgact tacagcgttc 99960
accaatgtga ctattcccaa gtgatccaga tggctgatga catagtaatt tgtacatttg 100020
ctgagacctg atctgagtag gtatgtaaca taactgaggg agagcaagtc catttgccga 100080
aagaaagcct agcatatgac ccaggagcca catcttcact cagccttgtt gctaggtttg 100140
gcttagcata tataatagca tagcatgtat aatttatgac aaaaaattat actttgcact 100200
ttttaattag aacattcaaa atgatctcag gaagtggcac cagagatcat cagtggtcta 100260
ctgtacttcg tgtgtatgtg tctgtgagta tgtatgtgtt tgtgtgtgtt cccacattct 100320
aaggcatgtc ttttacaggt tagtagaaaa tgttgataga aaattataga tttcaacatc 100380
taaaacacag taggtcacta cattgttaaa acttggaatt ttttatcttg ttgtaaagtc 100440
aggccaacca aacctaaaat actgctacat tgaaatagtg caaaatattc aaaatactat 100500
agttatagat ttggtagtag gactgtacca gacctgtcac tctatacaag acttatgcct 100560
tgccctttca cttacctgtt cccttttaca tctatcttac tagatgtaat gctataaatt 100620
atatttctaa tatattataa tttatcatgt attataatgt atcaaatatt acaaattatg 100680
ttgcaactcc ccttaccttt cgtctgcata ttgcctcaga aagaacagat ggatccaaca 100740
gacttcaacc acaggccctt agtgacaaat agctcttaat gctgggcttg ccactttgat 100800
gcatttctaa agttatagaa tgttaaatgc accaagtcct ttggtcattt tatttctacc 100860
ttagatctaa gccataacta tactttccca aaaattaaag tttgaatttt aacttaacca 100920
tatataattg gaaaaggagg ttgggttcgt taagtgtaat tttatcatgc tttattatcc 100980
tttgggcatt ggatacagca gaacatgcca atttctatgg cttctcatgt gacagaatat 101040
acttactagg atgcaattaa atactcctca gagtatgtaa acaataaatg taatcattac 101100
attattttta tattgttctt tcttatgcat aatagtaaga ctgaaaatat agtgttattt 101160
ctgaaatatg catattgttt tgcttttgat gattaaataa cattgtccaa agttttaggt 101220
tttttgaaat cttatatttt ttaacaaaat atctagcctt tccaaaacaa gacctcaata 101280
attcgtttaa gacccagagt tgttcctctc cacatagatc tcttaaaaag gcagaggatt 101340
tatgacctca agagaaatca gagtatccaa agtttgcttt aattcaatgt tttaaaaata 101400
aaattcctta gattttatca aaaattgaga ttagtttgat tttgaatcag atgccctttg 101460
ctccccaccc caaaatggca ttatgagcag actaggaatt gataatagaa aattgaacat 101520
atgaaatata tctttacctt gctttttaac aaggtattca tgtctatcgc cttcattttt 101580
aagtgcatca ataaaataca tggtaattct cttagtgaaa tatactatct acactatgta 101640
cacactcccc tgtctgaggt agagaagtag agaatattca catttttgaa acgtctatgc 101700
tatttttatt taaatacgag ttctgggctt gatttcattt tggaacacgg gtgtgtgctt 101760
aagttgaacc tttttttcct cttaagtcaa agttcttttt tagtttcttc ttttatcttt 101820
ttggctacta tctctctcct tcatcctcct ggtgtgagtt gttgagtgaa ggtattaatt 101880
ccattatttg aggctaagtg acattgttca ataatgcagc aaaacaatgg ttctacccaa 101940
aatatcttca agtgtaaaag cagtgggcaa aagagaaagt gcgcttctgc tgctttgaat 102000
gtttaaggct gtgaaagttg atcacacaaa ttgggtcatt cttgttatac ccaactaaaa 102060
caatcaagaa gcctgggagg aaaagcattc aagaaacatc acattgctcc aaaagtgtaa 102120
ttttctacaa gtccgcatgc tgaggctgcc tgttgtaacc tgggaccaat tttttctgta 102180
actgctgaaa aaacttgctg cagctctagg actaattttg cccaccactg tcactcacca 102240
attgaagctt actagctccc cagaaccttt ctagtgccaa tgaactttct caaagagcag 102300
cgtgtatcat ttctcttttt cagaacacct ccaacctcct ctttgttctt tgggtatacc 102360
aaagaccaac cagccttgaa tttcaatttt tcttcccaca taaaagtttt aatttagaaa 102420
tgtatctcta catttctaac tttgacaaag catagatacc agataattga tgaaaccttg 102480
ctattttaac gatcaccatg gattacttcc cagtgtcttc agataaccct caacatttgc 102540
caacatttga tggacttcaa aatgagcata tcttttttaa aaaaaattat tcacactgac 102600
agcaagtaca ttggtatact ctatattaaa ttataccaca gggtttacaa acaattggtg 102660
atgtcgggca gtggtttcca aggaacatac ttaacaagac actcacaagg ccctacaaac 102720
ctgcattttt aacaagggcc ctagatgatt ctagaagagt gtggtttgga aagcaatttt 102780
tgcctttatt atgtgtcatt ttaaatatat ttaaaattaa agttataagt catagaattg 102840
aataaagata atttccttac agaaagtatt actaggtatc taaatacaat atggttcaaa 102900
acaggaaatt taaaaagatt atgtaaattc tgtagttgta ttcctaaaga cagtagctga 102960
aattttttcc tacttctcct tgtatcactt cccttttcct tcactttcac ttccctggaa 103020
ttgtacttcc caataagcta ttagcagtga aggaagcttc gtctcatgat ctgttttata 103080
gagcacttca gctgggacga gtacgaaatg ataatcagtt atatcagcta ttcaacccta 103140
caggtttatt taaaaagaac ttgaataagc tttttaggga gaaagaggtc agtctcagcc 103200
atttctgttt cctaatatag cttttaagtc tttccttatt agcaatgagg gtcattccat 103260
tgtaattttt tgataaccat ttttctttct gtgtgtcaaa tgcagatata agatactgaa 103320
ctgagtctat ttcactgttc gtaaaacaat cccatttgaa aaaaaaaagt ctacagctat 103380
tccagggata gggcctagta gagagagaat aaaaggtatt ttcttactat gtctctatat 103440
cctaccctgt aggttctctt attaagcata caggcatata ccaaaatcca gacgtttttc 103500
tcatttattt tattgcccta acatattctg ggttaatata atatcataat gaaaatttga 103560
gaaaaaattg attttttcaa aagtgtttaa catttgttat attggtagtt ttttttcttg 103620
tttgtggtaa aaataaatag aaggtgcact tcacaccttc aagtatgatt atattttgaa 103680
aacaagtcat gaatactcat aaaatgcaaa ttttaatgtt ctttttttgt tacagccaaa 103740
ctatattagg cacagttgta aattggagtt gaaatttaat atttctttat agataacaat 103800
gtttttagaa ataggtttat gaaacagtaa atatacaggt atagggataa aattgtgtct 103860
gatggtcata tgaagtgttt gttgttatat tctccttgga atagctgcca aatattttag 103920
tatgcttaaa atctacgaat gtgatagagt caacaaattt agatcacata ttcagaaaaa 103980
catagttaga gaactaacta ttgaaatgag catacagcag tcttccttta tctacaggga 104040
tacattctga aacccccact aggacacctg aaattgcgga tagtagcaaa ccctacatat 104100
actgtttttt ccaatgctta tgtacctatg aaaaagttta atttataaac taggcacagt 104160
aagagattaa caacaataac taataacaaa agagaacaat tataataata tactgtaata 104220
aaagttatgt gggtatggtc tcgctttctc tttccctctc tctctgtctc taaatatctt 104280
agtattttgg ggttgcaatt ggtggtgggc aactgaaacc atggaaaaca aaaccacgga 104340
taaaaggaga ctactgtata tactttttaa aactgatgaa atattaaact catgtttctt 104400
ctatatccca cccatttccc ccacccaaac ctagatagat atcttatttg atctgtaaac 104460
atttaattaa tttgtaaaag ttaagaactt tttgaagtaa aactgcaata tatcatcaca 104520
cctaaagaaa taaacaataa ttcttaaata tcaagtcagt gttcaaattt ccccaactac 104580
ctcatatgtg ttttccattt gcttatgtag ggttcccaat gagaatgaaa taaagttctt 104640
aggttgcaat tggctaatgc tctctcactt ctactttaag cggcaggttc ccactaactt 104700
ctttttagtt gcaatttact tattgaaatt agacgtattc tttgtcttgt gtagtttctc 104760
acagtgcaaa atttgctgat tgtagccact gttgtaagca atgaacatgt ttttcaccac 104820
cttatatttg ctgtaagttg tcagtgatag ttaaatgtta atcaaattca aattcggatc 104880
acgtagggct tttctttttt tgttttcttt ttctatttat atatttattt atttattttg 104940
agacggagtc tcactccgtc accaggctgg agtgcaatgg tgtgatctgg gctcactgca 105000
atctccacct cccgggttca agtgattccc ctggctcagt ctcccgagta gctgggacta 105060
taggagaacc accacgcccg gctaactttt tgtattttag tagagatggg gtttcaccat 105120
gttggccagg atgctataga tctcctgacc tcaccgatca tgtaggactt caattgtcga 105180
acaaacgaac ctttaatagc agttacacca ttaggatgac ctgatccaac atcgaggtcg 105240
taaaccctat tgtcgatttg gactctagaa taggattgtg ctgtcatccc tagtgtagct 105300
tgttcccact tgatgaagtt attggatcag tgaacaatag cccacttaaa ctagtacagt 105360
cttagtttaa gatggtgatg tgtatgtact tccatcagag ggcacataat acagtaaatc 105420
ctcacttaac ttcatcaata gtttctggaa actgtgactt gaagcaaaac aacatataac 105480
aaaaccagtt ttaccattgg ctaattgata taagcaagaa ttaagtccta tggcaaattt 105540
ctggacacaa aaacaccatc aaactcctaa ataaagataa atcacttctg acattaaaca 105600
ttgaaattaa tgtgagctat atatacgttt aagaaagatt aatacaaaca agtcaaataa 105660
cttacctaat tatttcggtg gaggccgcag gtggttggag cctatcctgg cagctcaggg 105720
agcaatatgg gaacccaccc cggacaggac gctgttccat tactgcaggg tgctcttgta 105780
cacacccact cacccaggct ggaaccatgc agacacacac actcacctaa cctacacatc 105840
tgtgtacatc cttcaaagtt cagccaaata acatataaac aaatccagta atatccatca 105900
gtcttagttc cgtcataaca actccttttt gatcatcaaa caacaaacag ggtaggtctg 105960
ccatatttac ttgtctggtc catatcaaaa ttttctaaca aattatatta gaaaatcaaa 106020
tctctgtcag tttcaaaatc atggaaaaaa atttgcctta tttcccttat acttggatat 106080
cctaacagta atctaaatat taatgagaaa gttaatgatg tcgtttcctt ctccctgttg 106140
taaagaaggt tttgctgtcc cgtttgatca ctaagactaa ttgacactca gaaaaagcat 106200
aggaaacttc tcagcatcac aaaagctctg tcatctagag aagctaggac ttgagctcaa 106260
gtcctgtgac atggaaggcc ttgtgcctag ccatcctgca gcagaggcgt atctaccaag 106320
aagtgaaaca ctacgaaaac agtatgttta ctccacattt taaagtgagg tagtttgggg 106380
tggttcatat tttatttaat ttatatatta tttggatttt ttttagttta taaaaagggc 106440
attggcaagg gcagaatgat ctgtaagctt ctctgcccac ctaccataag catgatcttt 106500
agtgtgacct tttcttactg ttagccattt tcttatactt ctgcgtccct gtcagtcact 106560
tccatgtgaa gacatgggga agctttttta catcagacat gttgttgaaa atcagccgcg 106620
ttggctgagg gattatttga tctctttctc caagtccctt taggctcaca ttgcctctct 106680
gttctttgaa ttttcactta cctttatctt cttataatta ctttgctgaa ataaatgcaa 106740
agcaacaaaa ggtatttagt gaagaatacc aacaaagcca tgaccatttc aggctgagtt 106800
ttgtagtatt ctttgtctag gaagagatac ctagaaaaat tttctgacca tgtatttgat 106860
tattttcctt caatatgtat agtctcagtc ttcaaatttc agaaaagaat ttgtttcttc 106920
attgtcattt aaaattaatg tgttaaatat gtatgctttt acattataag tggttataaa 106980
agttaaacac ttagaaaaaa agtcaaaata acatacatac tatccaacaa aataactttc 107040
atattttatt gtgttttctt ccaaactttt tacctttgcg tctgaattct gtgtaggttg 107100
tatctataat atagacaaca ctttatagcc tgctaaatat tataccataa ataggtagtt 107160
gttacataat tctcaggtaa tagtaataca ggtctttatc ataatctact gagtagttga 107220
atgataattt tttttaagac aaggtctccc tctgtcaccc aggctagaat gcagtggcat 107280
gcacatggct cactgtagcc tctacctccc aggctcaagt gatcctcctg cctcagcctc 107340
ccaagtggct gggactgtag gcatgtgcca ccatgcccag ctatttattt gtatttttag 107400
tagagatggg gtttcattgt aacagcccag gctggtcttg aactcctgga ctcaaatgat 107460
ccacctgcct cagcctccca aagtgctgaa atcacaggag tgaaccactg cacccagcaa 107520
taatttttta actcttcatt attcattgaa catttagtta acaattctaa aaattttgtt 107580
tcctgctgtc attgatcttg tgaaaaatat ctttggacta tagctgtgga ttatttccta 107640
aatagtaaat tacttgagca aaaagtttac atactttgag ggttgataac ccatgttgcc 107700
gcaatgtttc cccggaggca ttgtggagtt tagaatgcca gtagtaatat taaggtgtgc 107760
cattttcaag atccgtggcc aacatcccta tatgtaagat ttttccaaaa catggttctg 107820
atttttaaaa gtgaaaaatg ctacttcatc atgttctttt tgtgcttctt actttaaata 107880
ttagaatgaa gaaggagccc cacaggaagg aattctggaa gatatgcctg tggatcctga 107940
caatgaggct tatgaaatgc cttctgaggt aggagtccaa gctgaatctt tctaacaaga 108000
cagtaccaaa aacctgtcat tgtcacattt ctctttcatt agtgcttagt gagaatcatt 108060
tgctctctac atgctcatta cgtggacaac ttgcaagtta agaatagttt ttacattttt 108120
aaagggtcct taaaaaaaaa gaggaggagg aagatgaaga agaggaagaa aggatgtaaa 108180
agaaatcata tgtagtccac atagcttaat atacttacta cttgaccctt tacaggaaaa 108240
gtttactaac ccctgcatta gagaatatat ttttagaaac tttacattct aaaataaatt 108300
tctaaatgga aagttaggga aatcaatgga atgccaaagg aaggttatta ttttttgcca 108360
tacatgtcca atgggatgac gcatagtaaa ataaaagtta cccacacaag ttatagaata 108420
aaaagataaa tgcatgattt gcgacaattg atatattcca gtataatgtt ttaaacaaca 108480
caatatgatt gttaatttta ttttgattga aaatgaaagt atctttaata gaaaatgtat 108540
caaaagggaa attagaaaat actgttagat gaataaaact ggcccaagaa gaaacagtaa 108600
atctgaatag atttgtaaca cagcgaatag attaaattag taataaaaaa aaaaacctac 108660
ctgcaaagaa aatcccaggc cgagatggca tcactggtaa attctaccaa acatttaaag 108720
aggaattaat actaattagt taacaccaat taatatctct tacaaaacag aagaggagac 108780
atttcccaac taattttgtg agaccaatat taccctgata atcaaaacca aatgaagata 108840
tcacaagaaa agaaactata taatggctcc attaaaaatt gagttcaagt atgttgtagt 108900
ttggttatgt attattcctc acggcattat taaaaggcat gtcgaggatg ggcacagcag 108960
ttcacacctg taatcccgca ctttgtgagc caaagtggcc aggttacttg aggccaggag 109020
ttggagacca gtctggccaa catggtgaaa ccccatctct actaaaaata caaaaattag 109080
ccgggcatgg tggtacacgc ctatggttcc agctacttgg gaggctgagg catgagagtc 109140
acttgaaccc aggaggcaga ggttgcagtg agctgagatg gcacccctgc actccaatct 109200
tggtaacaga gcaagactgt ctcacacaga cacacgaaag gcatattgat aataattcaa 109260
cttatagaaa ttgagattaa attgtttgtt tgcctaataa gaatttccaa tattttgggg 109320
tcttttatgc aagacacagt actaaacaca atggaaaact atagagtaat tgacattacc 109380
aggacataag gagtttacag tctggtaggt ttgatgaaaa aaaatagaaa ttcattcatt 109440
catttcttca ttatgattcc tttaacaaac ataattgatt gtcttcgatg taccaggcat 109500
cacaggagca aaaatatata agacatacta aaaagtaaaa cattttaaag atctgtttca 109560
atcaatcagg agaagtttta ttgaggaggt aatgttgatc tgggtgggaa aaggtaagag 109620
atatagtagg tcaaaacaaa cagaggacat tctggcacaa gggaatatca gaagcaaagg 109680
catgtatgtc tgagcatgca aatggatatg tctgagaaca gtgaataatt atgactcaag 109740
cttaggaaca aggaaaatgg tgatagattg aatttgcagc tatgggtcaa agacaagtta 109800
tagagtatta ggataatctt gtcatttcag cttgtattct attcagaaaa caacttgagt 109860
tattgaagtt atgcttattt gtttgttttt aagcagaatc ctgatattat tagagttgct 109920
ctttaggagg aataatctga tccctttaat taaatccatt aatatttgtg ttgtggatgc 109980
tatccagata ctgtatggag agcttgaggt ttgaaataca agtaataatt gaagccatag 110040
atgaagacga aattttcaac tgggagagtg aaagtaggga aaatgtatct tgccttcaaa 110100
catcttaatt tccttctgag aattagagca tcttagtctg gaaaaggctt tatagacagc 110160
ttgattttgt tctcacattt tacaggtgaa gaaactgaga accagacagt ccaacttatt 110220
tgtcctacca aactaggtat atgatcatta aatggtgcat ccggatcaga acctagatat 110280
tttaactctg actactactg taattcactt ttatatcaga caagaaagac acaactatta 110340
aaaataagat aatatttgct gcagaatatt tgcaaaaaca ttgattgtaa attttagtgt 110400
aagtggggag ccatttccta tctcattggc tgtcagtgct gatgcgtaat tgaaacttat 110460
actaacagtg tgtgctgtct ttttgatttt tctaatatta ggaagggtat caagactacg 110520
aacctgaagc ctaagaaata tctttgctcc cagtttcttg agatctgctg acagatgttc 110580
catcctgtac aagtgctcag ttccaatgtg cccagtcatg acatttctca aagtttttac 110640
agtgtatctc gaagtcttcc atcagcagtg attgaagtat ctgtacctgc ccccactcag 110700
catttcggtg cttccctttc actgaagtga atacatggta gcagggtctt tgtgtgctgt 110760
ggattttgtg gcttcaatct acgatgttaa aacaaattaa aaacacctaa gtgactacca 110820
cttatttcta aatcctcact atttttttgt tgctgttgtt cagaagttgt tagtgatttg 110880
ctatcatata ttataagatt tttaggtgtc ttttaatgat actgtctaag aataatgacg 110940
tattgtgaaa tttgttaata tatataatac ttaaaaatat gtgagcatga aactatgcac 111000
ctataaatac taaatatgaa attttaccat tttgcgatgt gttttattca cttgtgtttg 111060
tatataaatg gtgagaatta aaataaaacg ttatctcatt gcaaaaatat tttattttta 111120
tcccatctca ctttaataat aaaaatcatg cttataagca acatgaatta agaactgaca 111180
caaaggacaa aaatataaag ttattaatag ccatttgaag aaggaggaat tttagaagag 111240
gtagagaaaa tggaacatta accctacact cggaattccc tgaagcaaca ctgccagaag 111300
tgtgttttgg tatgcactgg ttccttaagt ggctgtgatt aattattgaa agtggggtgt 111360
tgaagacccc aactactatt gtagagtggt ctatttctcc cttcaatcct gtcaatgttt 111420
gctttacgta ttttggggaa ctgttgtttg atgtgtatgt gtttataatt gttatacatt 111480
tttaattgag ccttttatta acatatattg ttatttttgt ctcgaaataa ttttttagtt 111540
aaaatctatt ttgtctgata ttggtgtgaa tgctgtacct ttctgacaat aaataatatt 111600
cgaccatgaa taaaaaaaaa aaaaaagtgg gttcccggga actaagcagt gtagaagatg 111660
attttgacta caccctcctt agagagccat aagacacatt agcacatatt agcacattca 111720
aggctctgag agaatgtggt taactttgtt taactcagca ttcctcactt ttttttttta 111780
atcatcagaa attctctctc tctctctctc tttttctctc gctctctttt tttttttttt 111840
tttacaggaa atgcctttaa acatcgttgg aactaccaga gtcaccttaa aggagatcaa 111900
ttctctagac tgataaaaat ttcatggcct cctttaaatg ttgccaaata tatgaattct 111960
aggatttttc cttaggaaag gtttttctct ttcagggaag atctattaac tccccatggg 112020
tgctgaaaat aaacttgatg gtgaaaaact ctgtataaat taatttaaaa attatttggt 112080
ttctcttttt aattattctg gggcatagtc atttctaaaa gtcactagta gaaagtataa 112140
tttcaagaca gaatattcta gacatgctag cagtttatat gtattcatga gtaatgtgat 112200
atatattggg cgctggtgag gaaggaagga ggaatgagtg actataagga tggttaccat 112260
agaaacttcc ttttttacct aattgaagag agactactac agagtgctaa gctgcatgtg 112320
tcatcttaca ctagagagaa atggtaagtt tcttgtttta tttaagttat gtttaagcaa 112380
ggaaaggatt tgttattgaa cagtatattt caggaaggtt agaaagtggc ggttaggata 112440
tattttaaat ctacctaaag cagcatattt taaaaattta aaagtattgg tattaaatta 112500
agaaatagag gacagaacta gactgatagc agtgacctag aacaatttga gattaggaaa 112560
gttgtgacca tgaatttaag gatttatgtg gatacaaatt ctcctttaaa gtgtttcttc 112620
ccttaatatt tatctgacgg taatttttga gcagtgaatt actttatata tcttaatagt 112680
ttatttggga ccaaacactt aaacaaaaag ttctttaagt catataagcc ttttcaggaa 112740
gcttgtctca tattcactcc cgagacattc acctgccaag tggcctgagg atcaatccag 112800
tcctaggttt attttgcaga cttacattct cccaagttat tcagcctcat atgactccac 112860
ggtcggcttt accaaaacag ttcagagtgc actttggcac acaattggga acagaacaat 112920
ctaatgtgtg gtttggtatt ccaagtgggg tctttttcag aatctctgca ctagtgtgag 112980
atgcaaacat gtttcctcat ctttctggct tatccagtat gtagctattt gtgacataat 113040
aaatatatac atatatgaaa ata 113063
<210> 56
<211> 147102
<212> DNA
<213> Intelligent (Homo sapiens)
<400> 56
agagctcgcc tccctccgcc tcagactgtt ttggtagcaa cggcaacggc ggcggcgcgt 60
ttcggcccgg ctcccggcgg ctccttggtc tcggcgggcc tccccgcccc ttcgtcgtcc 120
tccttctccc cctcgccagc ccgggcgccc ctccggccgc gccaacccgc gcctccccgc 180
tcggcgcccg cgcgtccccg ccgcgttccg gcgtctcctt ggcgcgcccg gctcccggct 240
gtccccgccc ggcgtgcgag ccggtgtatg ggcccctcac catgtcgctg aagccccagc 300
agcagcagca gcagcagcag cagcagcagc agcagcaaca gcagcagcag cagcagcagc 360
agcagccgcc gcccgcggct gccaatgtcc gcaagcccgg cggcagcggc cttctagcgt 420
cgcccgccgc cgcgccttcg ccgtcctcgt cctcggtctc ctcgtcctcg gccacggctc 480
cctcctcggt ggtcgcggcg acctccggcg gcgggaggcc cggcctgggc aggtgggtgt 540
cggcacccca gccccctccg ctccgggccc ggcgtcccct cccccgcggc ccgcgccgcc 600
gtccccgccc cgtgacccgc cgggctaccc ggggtgggct gggggccggc agcgcggggg 660
agactcgctc gggcctgagc cccgaggctc ggccggtggg cgcagccggg gtcctctggg 720
attgtcaggc ctgtccagcc tcccgcagca tccccgcccc ctcccccggc ggtcaagatg 780
gagggagcgg gcggcctccc ctccccacgc gtgttgggag gggttctcgg gtagcggcga 840
tggtcagccc cggctccccc ttccgcacga tcctccgccc gcagcgtggg gatgctcggg 900
cagctcctcc actcccggtt taggtgtgaa cgttggaggg gtctggaggc tgtggtggcg 960
ttttccggaa catgtccccc tccatggggg acatctctgg aggggagaag ttagggccgc 1020
gtcccccgtg ccggttaaag gggtaggcac cgggctcctc cggaatcatc agggtctgtc 1080
ggggctctct ccccgccccc tccgagtcct gggaaagatc ggaggacggg gtggagacaa 1140
gtgggccttg gcccccgcac ccctctgcgt tcgtgtccga ggcggcggcg ggggctcccg 1200
aactcccctg aaatcgtggg gctccatgtg gcctccggca gcgttccacc ctcccccacc 1260
tggggaaggg aaggggtggg gagtgcccgg ccccgtcccg gccttcctcc ttcccccgcc 1320
agacctctcc ggcgcgcggg tggtggccga tccgcattgc tgttcgaggc cgcagtggag 1380
aaggcgcctg tggaacatcg gtgggtgagg gctggaccca ggctggaccc tggagatccg 1440
gggtggcggt gctggtggca gggggcgggc accctgcgca cttatcccaa cccccgcccc 1500
aatttcggaa atgctaggag agagagattg cagcagggga cgtggtcggg ttcctgaagg 1560
cagaaaggcg ggtgtttact agcgtctttt tccctcctaa gccggggttg tagtaggggc 1620
tgggggctca gtgttgtccc ggctaactgg gtttgactcg agggtgtgtt tgtgcaggag 1680
ggcctgttgg gggtggcggg cggttgtcag ttcgtatttc acgaactaag aaaatgctta 1740
gtgttcaaag ggagaaggaa acgtcaatag actccattcc attgtggccg gtgtccttaa 1800
cttcgggagt gccgccagag cttaccaagg gcacgcaagt ccatttccct tgtgcctcaa 1860
gtccatccgt gttgtaggca ctactgtgcc ttctttaggc ctaggccgcc ggcttgacgg 1920
cgggtgaccg gcgtcctcct taaataggca tcttgggctt tggaaggtgg aataagagga 1980
tttttcattc acccgagttt tctttttgaa aacacatttt cagcaaccca tttccaaaga 2040
atttttattt acagcagaaa ttccccatca agaggaatca gctggttttt aaggaattct 2100
gctgccttca aagggggcgg aaacagtcgg ttatttgact ttacacgccc cgccccccct 2160
tccccttctc tgagtctgaa gcatcccaaa cactacttag ccaaactagt tcagatgaag 2220
tgatcgtttc cccaagtagg gtaacttcag tttccctttt tcgttggcat ctagcgaaaa 2280
atgaaaaaat ttaaaataca acttttatag aaaaggatgt attctgtttt tactttctta 2340
ggtattagga agagatttgg cagataattc aacatgttca aatatataaa cattaaaact 2400
aaggttatta agttgcattg actactaggc ttaaaaatta gattataaga gaatttgctc 2460
ctgagtagtt tgagtgatca aagatatttg gaatgtttta gtaccacaag gtcttttttc 2520
tgttccttga ggctttacaa caatttaagg ttaatttaga tttttccttg ctttaagttc 2580
ttttacttga gacctaaatg gcagccctta ttctttctga tgaataggtg aaattttgtt 2640
tactgtgttg gatttgtgta atgtgaagtt ttattcttga acagatcgtt aatgtacttg 2700
tagaattact ttgaatttga atcactttcc tgcattcctt gtaaataagt ttcagcttct 2760
agaatctcct cacttaggtt tgtgcgtatc aacagtgaaa ataagtctct gagagcaagg 2820
gtgaaaaaaa atgcagcatt cggtttgaca agtttcgaga tagcaaaata tgcttgaaag 2880
tctggaaatt cacatctgct ttaagaaaca tttcataatt tgactttgtg tgtgtgtgtg 2940
tgaatagttt ttcatgactt tcagaagtga tttattttgt tctttgttat atatattttt 3000
gaaggtggct gttttaggaa agataatgta atcacaatat tagaacataa ttttactgta 3060
atctaatttt gtgtgtgtgt gtgtgtgtgt gtgtgtgtgt gtgtgtgtgt tttggatgga 3120
atctcactct gtcgcccagg ctggagtgca gtggcctgat ctcagcttac tgcagtctct 3180
gtctcctggg ttcatttaag tgattctcca gcctcagcct ccccagtagc tgggattaca 3240
ggttcgtgct accacacctg gctaattttt ttgtattttt agtgaggacg ggattttgcc 3300
atgttggcca ggctggtctc gaactcctga cctcaagtga tccgcctgcc ttggcctccc 3360
aaagtgctgg gattacaggc gtgagctact gcccctggcc aatttttgta tttttagtag 3420
agatggggtt tcaccatgtt ggccaggctg gtctcgaact cctcctgacc tcaagtgatt 3480
cgccagcctc ggcctcccaa agtgccagga ttacaggcag gaatgagcca ctgcccccaa 3540
ccatcagtct aattcttatt tttgcttttt accttttcat ttttatgtag tagaggtgat 3600
tgtgtatgtt attttgtagt tagctttttt cccctgaacg ttgtattgta aatgtaaatt 3660
tttttttttt tttttgagac agagtctcgg tgtttgccca gtctgaagtg cagtggtacg 3720
atctcagctc actgcagcct ctgactcctg ggttcaagcg attctcccac ctcagcctct 3780
tgagtagctg gggctacagg aatgttccac cacgcttggc taatttttgt atttttggta 3840
gagacaaggt ttcaccatgt tggccagttt ggtctcgtac taccgacctc aggtgatgcg 3900
cccgcctcgg cctcccaaag tgctgggatt gcaggcgtga gccactgcgc ccggctgtaa 3960
ggtttttact taaccattct attgttggga attgggtttc cacttttttg ttatagatag 4020
tggtgcagtg aacattttta aatagctttt tgcttcagtg taattatttc cttagagaaa 4080
gttaccaaga gtggttttac tagttcagag ggcttcagga tttttatggc tcttgctagc 4140
ggtgctctat tattctttag aagacttgta ttacttccag tgtcaagaag gttgctcttc 4200
catggaatgg tttctttgta gtttgtcaaa tattgtgggg aatttttaaa ggaaaaattg 4260
catttttact gtcaagtgca tatattatta agtgcttttg ttagttactg gattattgat 4320
atttgagttt aatttggttc ctctgaggat ttaataaggt aatatatgtg aagatgtttt 4380
gaaacctgta accattatta ttaatgaggg tacttggttt atctgtcgtg ctgatagtac 4440
tgagtaaagt gcaggaatga aattcctgag gaactgttct aaagctttgt tgttgttgtt 4500
aacctttctt tttcatctga aagtgttttt tattagctgc tagcctatga ccaagttatt 4560
tttggtaact tttttgtaat ttcatggcac tattgggaat tttcgctggt tgactcttct 4620
tcttctacat tcccttcccc attaaaaata aaaatatgga tttacaattg ttactctatt 4680
cctaaaccta aataatatga cattagaatt gcttgggata caggattcag tctgaataaa 4740
atatttttct tttagtgatt ttcagcttag tatttttact gcttctttct cttgaggcat 4800
tgcaacttaa aaattgtgct gtttagccag gcgcctgtaa tcccagctac ttgggaggct 4860
gaggcaggag catcacttga gcccaggagg cggaggttgc agtcagctga gattgtgcca 4920
ctgcactcca gcctgggaga cagagtgaga ctctatctca aaaaaaaaaa aaatgtgctg 4980
tgatttaatg tagttgttca tcatgcttcc atttaaattt cagtgagact gttcatcttt 5040
tgcagttaaa tatcttgtag aagggcctaa aatatctacg ttgaatacag ctttattgaa 5100
gcatctatgt acatggggtt tttgggatga atcagtgaat aaagcaaaca tattgtcctt 5160
ttggagttta cattctaatg tgactaggca gacaatgaga cattaaatta ccagcctatg 5220
tataatagtg tataagagct atggaattag aagaaagcag attaaaggta tagggagtgt 5280
ggggagggga atgagttaca attttaaatg gattggggga acttaattga ggagctaaca 5340
tttgagcaaa gatttgaagg ttgggtattt agccgtttgc tttttatcta ggttaattag 5400
tcatgtggct tcattagtaa tttataaggt ttaaatggca tcatcctttg ttattctttt 5460
atgtgcacat tgatactaac catctctgaa gttagaccaa aaaagttaat tgacattgag 5520
ggtcattaga ggtaaattgt agatggctat tactaaccaa agagacatgt tttgtttttc 5580
ttttgggctt acgtatttta cctaattagt ttagtttttg tttcaagtat gtggagaaaa 5640
taaacttttt aagtttgggc caaaacttgc tttggttttc tttttctttt tctttttttt 5700
tttttaagag aaaaatgtaa gcctgtagtt gcttaaagat tccacattct gaaacagtga 5760
aaacatggga tcagtcatgg tgttcctttt tttggttaaa tgtaaacttg tattttcagt 5820
gttactctaa ttagcaatgg tttatacttc tacataaggg atgttaactc atattgtagc 5880
tatttaatag ccatatattt tgacttaaag gaggatctca aggccaggcg cggtggctca 5940
tacctgtaat cccagcactt taggaggctg aggcgggtgg atcacctggg gtcaggagtt 6000
tgagactagt ctggccaaca tggtgaaacc cccatctcta ctaaaaatac aaaaattagc 6060
cgggcatggt ggtgggcgcc tgtaatccca gcttcttggg aggctgaggg aagagaattg 6120
cttgatcccg gaggttgcaa tgagtgcgga ggttgcagtg agctgagatc atgccattac 6180
actccagcct gggcaacaga gcgagactct gtctcaaaac aaacaaacaa acaaaaaaag 6240
gaggatctca tttttttgtc ctaaatagct acagccgtgt tagaactgtc accttagcaa 6300
agtattgttt ttttactttg aaacgaattt taaggtttta gaagattgtt ctctagaatt 6360
acaattttct gttttgacta gtgatagtat tttgatgttg tgtaaatagt tgagcatgaa 6420
caaaacccta tttttttttt tagctatttc aagtgattgt gacaacttca acggagatgt 6480
aaacagttta ttaacagtca cacctattat cttttttttt tttttttttt tttgagacgg 6540
agtcttgctc tgtcgcccag gctggagtgc agtggcacga tctctgctta ctgcaacctt 6600
tgcctcccgg gttcaagtga ttctcctgcc tcagcctcct gagtagctgg gtctacatgc 6660
gcacaccacc acgcctggct aatttttgta tttttagtag agacagggtt tcaccatgtt 6720
ggctagaatg gtctcaaact cctgacctca ggtgatccac ctgcctcagc ctcccaaagt 6780
tctgggatta caggcatgag ccaccgtgct tggccgctgc cgtatctttt taaatgaaag 6840
tacttgtgtt ttttttgttt ttttccaaag gatatctggg tcatctatga tgttactgtt 6900
accatctaag ggtttttttg tttgtttttg agacagagtc tctgtcgccc aggctggagt 6960
gcagtggcgt gatcttggct cactgcaacc tccgcctccc aggttcaagc aattctcctg 7020
ccttagccct cccgaatagc tgggattaca ggcacccgcc accatgcctg gctaagtttt 7080
gcatttttag tagatatgga gtttcaccat gttggccagg ctgctcttga actcctgacc 7140
tcaggtgatt cgcttgcctc ggcctcccaa agtgctggga ttacaggcgt gagccacccc 7200
cgcccagcct catgagctaa ggtgtttttt ttttttttga gacagttttg ctctttccca 7260
ggctggagtg cagtggtgca atctcagctc actgcaacct ctgtttcccg ggttcaagcg 7320
attctcctgc ctcagccttc tgagtagctg agattacagg tgcctgctac cccactcagc 7380
taatttttgt atttttagca gagacagggt ttcaccatgt tggttaggct catctcgaac 7440
tcctgacctt aagcgatcca cctgccttgg cctcccaaag tgctgggatt ataggcatga 7500
gccaccgtgc gcagcctacc ctgtctctta aaaaacagta acaacaacaa caacaacaaa 7560
aaatcctaaa tcttaaaaat ggaaggcaaa aactctaagc tttgagagat taggggactt 7620
gcccaaagca atatttgtag gattttatta cacctctccc tttatttatt tttttagagt 7680
caaggtctcc ctctgtcacc caggctggag tgcagcctca atctatgggg ccaagcattt 7740
ctcctgtctt agcctcctga gtagctggaa ctacaggtgt acaccagctg gctaacattt 7800
aaattttttg tagagacagg gtcctgccat gttgcccaga ttggtctcaa actcctgggc 7860
tcaagtgatc ctcctgcctc agcttcccaa agtgctgaga ttacaggtgt gagccactgc 7920
accgagcccc ctccctttat ttttattttt aaattttaag ttctggggcc cctcccttga 7980
aataaataga aacgtaatat atacacaaga tcatgctgtg tattttaagg caatggtcct 8040
caaccttttt aacactaggg accggttttg tggaagatgg tttttccata ggggcagggg 8100
atgattttga gatgaaactg ttccaccggc cgggcacggt ggctcacgcc tgtaatccca 8160
gcactttggg aggccgaggc gggcagatca cgaggtcagg agatcgagac catcctggct 8220
aacatggtga aacccccctc tactaaaaat acaaaaaaat tagctgggcg cggtggaggg 8280
cgcctgtagt cacagctact ccggaggccg aggcaagaga atggcatgaa acccgggagg 8340
cagagcttgc agtgagctga gatagcacca ctgtacttca gcctggggga caaagtgaga 8400
ctccgtctaa aaaaaaaaaa attgttccac ctcagatcat tatgcatttg ttagattctc 8460
ataaagagca tacaacctac atctcttgct atatgcagtt cccagtaggg tttgtgcttc 8520
tataagaacc taatgctgca cctgatctaa caggtggggc tcaggtgcta atgctcacac 8580
agctcctgtt gtgcagtctg gttcctaaca ggcctgtttt ttttttttta attagatgga 8640
gtctcgctct gtcaccaggc tggagtgcag tggcacgatc tcagctcact gcaacctctg 8700
cctcccgggt tcaagcgatt ctcctgcctt agcctcccat gtagttggta ctacaggcgc 8760
acactgtgat gcccagctaa tttttgtatt tttagtagag acggggtttc accatgttgg 8820
ccaggatggt gtcgatctcc tgaccttgtg atccgcccaa cagcctccca aagtgctgga 8880
attacaggcg tgagctgctg cgtccggccc cctaacaggc ttgttttatg gaatacagtc 8940
acggacagta cttgcccttc aggatatctt tttgtaacct tgattttggc ttgctaaaat 9000
aggaggtcta ttttcttttc tttgttttta atgtatgtgg ttctgtactt acgtggtgtg 9060
aaatctacat aaatgttaaa tccttggtta tttatttatt ttgagacaga gtctcactct 9120
gtcacccagt ctggaaagca gtggcataat ctcggctcac tgtaacctcc acttcccagg 9180
ttccagtgat tctcctgcct cagcctcctg agtagctggg attacaggca tgcaccacta 9240
cacctggcaa atttttgtat ttttttttag tagagatggg gtttcaccat gttggccagg 9300
ctcgtcttga actcctgacc ttaggtgatc tgcctgtctt ggcctcccaa agttttggga 9360
ttacagcatg agccactgcg cctcgcctta tttttttgag acaggttcta gctctgtcac 9420
ccaggcggga gtgcagtggt gccatcatgg ctcattgcaa cctcgagttc tcaggcccaa 9480
gtgatcctcc tatctcagcc tcctgagtag ctgggaccac aggcatgcgc cactatgccc 9540
agcaaaattt ttgtttcact ctgttgccta gggtggggtg cagtggcagg atatcggctc 9600
agtgcaacct ctgcctcttg cgttcaaatg attctcatgc ctcagcctcc cgagtagctg 9660
ggattatagg catgcgccac tacacctggc taatttttgt attattggta gagatggggt 9720
tttatcatgt tggccaggct ggtctcgaac tcccgacctc aggtgatcca tataccttgg 9780
cctcctgaag tgctggaatt acaggcataa gccactgcgc ctagcttttt tgtttgtttt 9840
tattttgtag ggacagagat tttacctgtt gcccaggatg gccttgaatt cctgacctca 9900
aacaatttgc cctccttggc ctcccaaggt gctgggatta caggtgtgag ccactatgcc 9960
tggctggttt tttaaattat tattattgtt tgtgtgtgtg tgttgcagga tcttaccctg 10020
tcacccaggc tggaatgcag tgatgtgatc tcggcttact gcaacctccg cctcctaggt 10080
tcaagtgatt gtcctgcctc agcctcctga gtagctggga taacagctgt gtgccaccat 10140
gcctggctaa tttttgtatt tttagtagag atggggtttc atcatgttgg ccaggctggt 10200
ctcgaactcc tgaccttaga tgatccaccc gcctcgtcct cccaaagtgc tgggattaca 10260
ggtgtgagcc accgtgacca gtttggttta gttttttttt tttttttttt tttttttttt 10320
ttttgagaaa tctcgctctg tcgcccaggc tagagtgcgg tgacacaatc tcagctcact 10380
gcaagctcca cctcccaggt tcatgccatt ctcctgcctc agcctcccga gtagctggga 10440
ctacatgcgc ccgccaccat gcccggctaa ttttttttat gcattttaag tagagatggg 10500
gtttcactgt gttagccagg attgtctcaa tctcccgacc tcttgatctg cccgcctcgg 10560
cttcccaaag tgctgggatt ataggcatga gccaccgcgt ccggcctggt ttggtatttt 10620
ttttatgagt ctgggttgtt tatgaaaact tgtcacagct gttaacctta actttttttt 10680
tttctttttt ttccgagacg gagtctcgct ctgtcaccta ggctggagtg cagtggtgcg 10740
atctcggctc attgcaacct ctgcctccca ggttaaagcg atttttctgc ctcagcctcc 10800
tgagtagctg ggactgcagg cacgcaccat ctcgcctggc taatttttgt attttagtag 10860
agatggggtt tcaccatatt ggccaggctg gtctggaact tctggcctca agtgatccac 10920
ctgccttggc ctcccatgcc tggcaacctt aactttttat ttgctggtaa ttatttgtgt 10980
ttgcattcat gtgaaaattt gaaattctca ttaacattta aagattctta catagattgc 11040
ttgtaatttt aaccctgaag ttgtgtcaag tgactttaca atgtcaattt gttttattta 11100
tttatttatt tatttattta tttatttttg tgataggatc tggctctgtt gctaaggctg 11160
gagtgcagtg ttgcaaatac ggctcactgc aacctctgtc tcccgggttc aagccatcct 11220
cccacctcag cctcccaagt agttggaact actggtgcgc cccacagtgc ctgcctagtt 11280
tttttgtatt ttcagtagat gtggagtttt gccatgttga tcttgaactc atggcctcga 11340
gtgatccacc ccacttaggc ctcctaacat gctggtgtta caggtgtgag ccactgtgtc 11400
cagcccgaaa atgtcagttt cgtgccatga ttaatagcta actacatttt gggaatgtaa 11460
taaaatttca ttctataatg aagtctttgt aaaactcatt agttgtggta tgaggcttgt 11520
cggcaatata agtgaacgtg gtttattttt attaactgta tcagaacttt agaatgttgg 11580
tctcctgaaa ccattgcctt gagaggcttt attgaacagt gttgccaatg atcagttttt 11640
ttttaaattt cctttttttt gagactgagt cttaccctgt tggccaggtt ggagtatagt 11700
ggtatggtca tggctcactg cagcctcaac atcctgggct caagcagtcc tcctacctca 11760
gtctcccgag tagctggaac tacaggtgta tgccaccatg cctggctttt gtatattttg 11820
tagagacagg gtttagccat gttgcccagg ctggtctcaa actcttaaat tcaaatgatc 11880
cacccaccta gttttcccaa agtgctttaa ttacatgtgt gaggcaccgt ggctggccag 11940
gtcaaatatt tttcattgac gtttttcata ttgcttttta aagtcatgtt aaaatattct 12000
taataatttt tctaagtgga attaatcttg attataattt tagtttttta taaagggcgg 12060
gttttgaaac aagtactgca tttttctttt cgggtttata aacatttgct gtggactttg 12120
tgcagttaac tattttcatt cctgaaacac atttcgaaat caggaattga agactaaatg 12180
tcttttcact gaagcttgag cagattttag aaaggggagt tctttttttt tttttttttt 12240
ttggtagaaa tgggggtctt gttatgttgc ccaggctggc ctccaacttc tgggcttaaa 12300
ctgtcctcct gctttagcct ctggtctgga gagttcttta tggcctcttt gagaactttt 12360
actttacaca tgattctatc tagctttctt ttctgatgta catattggca gcaagtagaa 12420
aagcaatgtt ttcagaggca gatatattaa cagcaatgag aaataacagt agcgtgatag 12480
aaagttgaaa gacttagctg ggtgcggtgg ctcacgcttg taatcccagc actttgggag 12540
gccaaggagg gtggatcact tgaggtcagg agttcgagac cagtctggcc aacatggtga 12600
aaccctgtct ctactgaaaa acagaaaaag ggccgggcgt ggtggctcac ccctgtaatc 12660
ccagcacttt gggaggttga ggagggcgga ttacaaggtc aagagattga gaccattctg 12720
gccaacaggg tgaaacccca tctctactaa aaatacaaaa aaattaaatg ggcgtggtga 12780
tgtgtgcctg tagtcccagc tactcgggag gctgaggcag gagaattgct tgaacccggg 12840
aggcagaggt tgcagtgagc cgagatcggg ccactgcact gacgacagag ggagactccg 12900
tctaaaaaaa aaaaaaaaaa aaaaaaacca gacttggggc tgggcgggcg cctgtaatcc 12960
cagctacttg ggaggctgag gcaggagaat cgcttgaacc cgggaggtga aggttgcagt 13020
gagctcagat tgtgccactg tgccccagcc tgggccacag agcagagtga gactctgtct 13080
caaaaaaaaa aaaaaagttt ggaagactgg tggctgggca tggtggctca cacctgtaat 13140
cccaacactt tgggaggctg aagcaggcag attacctgag cccaggagtt caagtccagc 13200
ctgggcaaca cagggaaacc ccatctcaac aaaaaatatt aatacaaaaa atttagccag 13260
tcatggtcgt gcacttctgt agtctcagct acttgggagg ctgaggcagg tggttcactt 13320
aagtctggat gtcgaggtga gccatgattg caccactgca ctccagcctg ggcgttaaaa 13380
tgagacctta tctcaaaaaa acaaagcaaa gagcctggga actactaaaa tgggaactac 13440
taaaaaacag acacaagagc tcaacaagta taccattctg ggaggttttt tttttttttt 13500
tttttttttt ttttgagatg gagttttgct cttgtcaccc aggctggagt gcaatggcgc 13560
catctctgct cactgtagtt ccgcctccca ggttcaagca gttctcctgc ctgactcctg 13620
agtagctggg agtacagata ttggtcacac accgggttaa tttttgtatt tttagtagag 13680
acggggtttc cccattttgg ccaggctggt ctcgaactcc tgacctcagg tgatccgcct 13740
gcttcagcct cccaaagtgc cgggaccaca ggcgtgagcc accgcacctg gctttttttt 13800
tttgacatag aatcttgttc tgttgcccag gctggagtgc aatggtacaa tcttggccca 13860
ctgcaacctc tgcctcccag cttctagcga ttttcctgcc tctgactcct gagtagctgg 13920
gattacgggt gcccgccacc acacccggat aatttttgta tttttagtag agatggggtt 13980
ttgccatatt ggccaggccg gtcttgaact cctgacctca gatgatccac ctgcctaggc 14040
ctcccaaagt gccgggatta caggcgtgag ccaccactcc cggcctggga gttttgactg 14100
taagtttata gctgtatatc ttaggcccta agggcattac tgttttatag cacagtgtag 14160
ttagttaatg tgctcataat ggtgactcat aacaccaggt taaatgattt tttatatctc 14220
ccaaagaagt atttttcaat ctgcagatca tgacccctta gtagattgtg aaacacatta 14280
gtggattatg acaagcattt ttagaaaaat gaaaaagaat aagaagtgtt aggatgcatt 14340
gcattattga aataattgtt tttgagatgg agtttcgctc ttagttgccg aggctggagt 14400
gcaatggccc gatctgcctc ccgggttcaa gtgattctcc tacctcagcc tcctgagtag 14460
ctgggattac agacatgctc caccatgcct ggctaatttt gtatttagtt ttagtagaga 14520
tggggtttct ccatgttggt caggctggtc ttgaactcct gacctcaggt gatccacttg 14580
cctcggcctc ccaaagtgct ggggatacag gcatgaaccc ctgtgcccgg cctaattttt 14640
gtatttttag tagagatggg gtttcaccat gttggccagg atagtcttga tctcttgacc 14700
tcgtaatctg cccacctcga ctcccaaagt gctgggatta caggtgtgag ccactgcacc 14760
cagctgccaa gaattgtttt aagctttggt ttgagttaat gtatatatac cgcattgtaa 14820
ttcaaaatgt aatttttggc caactctggg cacattgcct atggactagt cctgctctgc 14880
cacgagcagc aacagttcaa tgaatttttt tttttttttt tttttttttt ttttttttga 14940
gacagggtct ctgtcaccaa ggctagaatg tagtggtgca gtctcggctc actgcaacct 15000
ctgtttcctg ggctcaagcg atcctcccac ctcagcctcc tgagtagctg ggagtacagg 15060
agcacgctac catgcctggc taatttttgt attttttgaa gagatgaggt tttgccatgt 15120
tgttcaggct agtcttgaac tctggagctc agatgatcca cccaccttgg tgtccagaaa 15180
tgctgggatt acagggatga gccaccgtgc ctagccaaaa attttttttt aagtaatttt 15240
ttattgatat agtcaaaaaa gttactgctt tagagccaga gaaacgcagt aaaaggattg 15300
agaaagagtt ttgaggttat atctaagcta gggttgtcag atttggcaaa tagaaataca 15360
ggacactcag ttaaatttga atttttgatg aacattgacc agttttttag tataattgtg 15420
tattaaattg catagaaaaa agttatttat ctaaagttga aatttaactg agcatcttgt 15480
attttatctg gcaactccag tctaagctgg aatcatggtt cactgttttt tttttttttt 15540
tttttttttg agtcggagtc ttgctgtgtt gcccaggctg gagtgcaatg gtgcgatctt 15600
ggctcactgc aacctccacc tcctgtgttc aagtgattct cctgcctcag cctcctgaat 15660
agttgggatt acaggcaccc accaccatgc ccagctaatt tttatatttt tagtagagac 15720
ggggttttcg ccatgttgtt caggctggtc ttgaactcct gacctcaggt ggtccgccca 15780
cctgggcctc ccaacgtgct gggattacag gcatgatcta ccgtgcctgg ccatggttca 15840
ctcttcagta actaaaattt aagctctatg aaagcaggaa ctttgttttg ttcactattg 15900
attgtatccc tatttcttga atggttggca cttaactgct tggtcacatg tttgaatggg 15960
caagttactc agccactctc aggcttagtt tatttaccta ttaaaagaga aagaatatct 16020
tccttggctg ggcgcggtgg ctcacgccta taatcccagc actttgggag gctgaggcgg 16080
gtggatcacg aggtcaggag atcgagacca acctgggcaa cattgtgaaa cctcatctct 16140
actaaaatag aaaaaattag ctgggcatgg tggtgcgcat ctgtagtccc agctactcga 16200
gaggctgagg caggggaatc gcttgaaccc aggaggtgga ggttgcagtg agccaagatt 16260
gtgccactgc actccagcct gggcgacaga acgagactct gtctccaaaa aaaaaaaaaa 16320
aacaaacaaa aaaaaaaact gagatactgg ccgggcgcgg tggctcgtgc ctgtaatccc 16380
agcactttgg aaggccgagg cgggtggatc acgaggtcag gagatcgaga ccgtcctgcc 16440
taacatgggg aaaccctgtc tctactaaaa atacaaaaaa ttagccaggc gtggtggcgg 16500
gcgcctgtaa tcccagctac ttgggaggct gaggcaggag aatggcgtga acccgggagg 16560
cagagcttgc agtgagcgga gatggtgcca ctgcactcca gcctgctggg cgacagagcg 16620
agactccgtc tcaaacaaac aaacaaacaa acaaaaaaac tgagatacta aagtcttaat 16680
attttctgtt tttatgtatt tattttttga gatgggatct tgctgtattg cccaggttgg 16740
agtacagtat tgtgatcatg gcttattgca gcctttaact cctgggttca agtgatcctc 16800
ccacctcagc ctcctgagta gctgggacca caggcacatg caacatcaca ccctgcagtt 16860
cttttttttt ttttgagaca ccgtctcgct ttgtcaccca ggctgcagtg cgtggtgcaa 16920
tttctgctca ctctaacctc cacctcccga gttcaagcag ttctgcctca gcctcctgag 16980
tagcttggga ccacatgtgt gtgccatcat gcctggttaa ttttttgtat ttttagtagt 17040
gacagggtct taccatgttg cccaggttgg tctcaaactc ctgagctcaa gtgatctgcc 17100
cgccttcgcc tcccaaagtg tctgcgccct acaatttaaa aaaatttttg tagagacagt 17160
ctcactgtta cccgggctgg ttttgaactt ctgccctcaa gtactcctct tgccttggcc 17220
tcccaaagta ttgaaattaa ggccatgagg cagcacaccc agcctaaatt cttcttatgt 17280
tctgttcttg gcacatagta gatgttcaac aatgtagagt caaacgcatt tggagttgga 17340
atggctctgg tgtttttttt ttttttttaa accagaaaca cgtgcagttt attgaatgcc 17400
attgtagaaa agtgtgtgag gataaacggc tgatagagaa cttggctctg ggggcagggc 17460
gaggaatgga gggtggatgg agtacatggg aatcagatca cgggcagagc tcctggccta 17520
gataatgcct cctgatctgt tgatagactt gaaagatcaa cactgggatg atgctgagca 17580
gaatggtcgt aatgatgcgc acaatcaggg cccagatgtt caggcacttg gcggtaaagg 17640
cataggcctg ggccctgatc aggtcgccaa ccatcttctt gtccctagac ttcacggagt 17700
aggccaatgc tatgaagccc aggcagcagg agttcatgaa gtgggtgttg aacagggacc 17760
agacgacatg gtcgggcacg gagttctcgc tgtggatggg gatcacggtg gacattgggg 17820
gagcagggtt gtggggtgcc cccagcacag ccacctcttg ctcctccttg agcatctcat 17880
agttaggggg atggccgatg ttggcaggag tgaagaggtt tggacattgt ggttcatggt 17940
gtccagggaa gaccagctgt ggtcgggttg ctggggtggt tctcagtggg cccctccctt 18000
tccctggtag tttggatttc tctggctctg gtggtttttt agtactcatt ctatttacgg 18060
gtgaagaaat tgagaccaag agggttattt accagagtat ctcatcattg gctgcataac 18120
tggcattaga atctgatgta cttttatttc taatacattt cttttttttt tttttttttt 18180
gagatggagt ctcgctctgt tgccgagcct agagtgcagt ggggcaatct tggctccttg 18240
caacctccac ctcctgggtt caagctattc ctgtctcagc ctcccaagta gctgggacta 18300
caggcacctg ccaccacagc cggctaggtt ttgtatttta gtagagatgg ggtagcacca 18360
tgttggccag gctggtctcg aactcatgac ctcaggtgat ccacctgcct cggcctccca 18420
gtgctgggat tataggcatg agccaccatg cctggccttt ctttgtcgtt tcctttcttt 18480
ctcttcatcc ctcctctcct tttttcccct ccccgctgcc tcctcctgtc ttcccttctt 18540
tccttccttt ctctcctttt tattttttcc tttctttttc tttctctgtc tctcccaacc 18600
cttcctctct ccctccctcc ctccccttct ctctcccccc ctccctcccc ttctctctcc 18660
ccctcccctt ttgttcctaa gagacagggt ctccttatgt tgctgaggct gaccttgaac 18720
tcctgagccc agatgattct gcctccttag tagctgggac tacacccacc tcccgttccg 18780
ttgtcatctt tttttttttt ttcttttttg gagacagaat cttcctctgt tgctcagggt 18840
ggagtgtagt ggcacgatca tagcttactg taactgtgta acctcgaatt cttgggctca 18900
agcaatcatc ccatcatccc acctcagctt gctgagtacc tggggctaca ggtgtgtacc 18960
accatgtccg gctaattact tttcttattt ttaatttttc ggagatagga tcttgctctg 19020
ttgcccaggc tggtgtcaaa ctcctgggct caagtgaaac tcttgccttg gcctcccaaa 19080
gtgttgggag ggattacagg catgagccac tgcacccagc ctcctctttc ttcccattta 19140
actcctaacc acaccgaact ttctgtctgc agagaggagc attggtcagc agttcacaaa 19200
atggctaggt gtgatggcgt gcacccatag tcccagctac ttggggagct gaggtgggag 19260
gatcgctgga gcccaggagt tcaaggccct gggcaacaca gcaagacctt atctctggct 19320
gggcccagtg gctcacgcct gtaatcccag cactttggga ggctgaggtg ggtggatcac 19380
ctgaggtcag gagttcgaga ccagcctggc caacatggtg agaccctgtg tctactaaaa 19440
gtacaaaaat tagccaggca cggtggcgcg ctcctgtaat cccagctact cgggggggct 19500
gagacaggag aatcacttga acccaggagg aggaggttgc agtgaaccaa gaacacgcca 19560
ctgcactcca gcctgggtga catagtgaga ctcttatctc aaaaaaaaaa aaaaaaggtc 19620
gtctgtacta ttgcatgtta gtagtttctt tctgcttatt gttgagtagt agtctattgt 19680
atgcatgtac cagtttgttc atctagtggt ggacattgag ttagcaggtt ttggctatta 19740
aaaataaagc tggaggccgg gtgcgatgtc tcacgcctgt aatcccagca ttttggaagg 19800
ccgaggcagg cggatcacct aaggttggga gtttgagacc agcctgacca acatggagaa 19860
accccatctc tactaaaaat acaaaattag ccaggcgtgg tggcgcatgc ctgtaatcct 19920
agctactcag gaggctgagg caggagaatc gcttgaaccc gggaggcaga ggttgtggtg 19980
agccaagatt gcaccattgc actccagcct gggcatcaag agtgaaactc cgtctcaaaa 20040
aaataaataa ataaagctgg tatgaatatt tatgtacagg ttttgtgtga acatatgatt 20100
ttatttctct tggttggaat gcatagaaat gagattgctg ggttttgtgg caagtgttta 20160
tttttccagg gtacatataa tcctgtgagt gtttatttaa ttttaaaagt aattgctaaa 20220
ctgtttgcta aagtgactgc tatattttct ttccctagca gtgtatgaat ttttttttga 20280
ggcagggtct tgctctgtca cccagggtgg agtgcagtgg tgcgatattg tctgactgca 20340
acattgacct cctgggctca agtgatcctc ctgcctcagc ctcctggctg ggaccacagg 20400
catgtaccac cacacctggt agtttgcttt gatttttagt agagaagagg tctcactatg 20460
ttgccctggg tggtgttgaa ctcctgggct caagtgattc atctacctca gcctcccaaa 20520
gtgctgggat tatagatatg agcccctgtg cctggcctca ttgtggtttt aatttgcatt 20580
tccctaatgc ccagtgatat tgagcatttt ttcatgtgtt tatttgacat tcataccatc 20640
tttggtgatg agaaactatg tttatgcatt gcttaatgat ggggatgtgt tttgagaaat 20700
tttttcggtg atcttatcat tgtacaaata tagagtttac ttacacaagc ctagatggta 20760
tacctactag acacataggc tgtcgtacag agtattactc ttaggctaca aatctgtata 20820
gcatgttgcg gtactgaaca ctgttggcag atgtaacata atgttaagta tttgtgaatc 20880
taaacatatc taaacataga aaaggtgagt aaaaatacag cgtaaaagat aaaagtggta 20940
tatctgaata ggtcacttac catgaatgga gcttgcagga caggaagttg cttgggatga 21000
gtcatttatc agtggtgtgt gaatgtgcag gcctaggaca ttactgtatg ctactgtaga 21060
caaacactga acagttagga tacactaaat tgataaatat ctttcttatt ttgttttttg 21120
agatggagtc tcgctctatc gcccaggctg gagtgtagtg gcgtgatgtt ggctcactgc 21180
agtctctgcc ttctgggttc aagcgattct cctgcctcaa cctcctgaat agctgggatt 21240
acaggtgcgt gccaccacac ctggctaatt tttgtatttt tagtagagac gggggtttca 21300
ccatgttggc caggctggtc tcgaactcct gacctcaggt gatccacccg ccgtggcctc 21360
ccaaagtgct gggattacag atgtgagcca ccgcacctgg ccagagatga ggtcttgctg 21420
tattgcccag ggcgttgaac tcctgggctc cagcaatcct cccacctcag cttcccacgt 21480
agctgggact gtgggtgcac gccatcatgc ctagccgttt tgtgaactgt tgaccaatgc 21540
tcttttctgc agacagaaag ttcactgtgg ttaggagtta agacttttaa cctctgacct 21600
caagtgatct gcccaccttg acctcccaaa gtgctgggat tacaggtgtg agccatcacg 21660
cctggtcaaa aatatctttc tttaagagta aatttacctt aacttactgg ttgatcattg 21720
tatataggtc tgttgttaat tgaaacatgc gggccgggcc cggtggctca tgcctgtaat 21780
cccagcactt tgggaggccg aggcgggtgg atcacaaggt caggagatcg agaccatcct 21840
ggctaacacg gtgaaacccc gtctctacta aaaatactaa aaattaaccg ggtgtggtgg 21900
cgggcgcctg taatcccagc tactcgggag gctgaggcag gagaatggcg tgaacccggg 21960
aggcggagct tgcagtgagc cgagatcgtg ccactgcact ccagcctggg caacagagcg 22020
agactctgtc tcaaaataaa taaataaata aataaataat tgaaacatgc ggtgcatgtg 22080
tttatttgcg atctgacttg tttggaaata tttgcattat cttccttcta gatttagagc 22140
atcttgacag taggaacaag tgttttgtac aactttgtat gcttagtaag ttatcaatta 22200
acttgtcgtg gccaggcgca gtggctcacg actgtaatcc cagcactttg ggaggccgag 22260
gcgggcagat cacctgaggt caggagttcg agaccagcgt ggccaacgtg gtgaaaccct 22320
gggtttgttt gtttgtttat ttatttattt attttttgga gacggagtct cgctctgtcg 22380
cccaggctgg agtgcagtgg cgtgatctcg gctcactgca acctccgact cccaggttca 22440
tgccattctc ctgcctcagc ctcccaagta gctgggacta caggagcccg ccaccatgcc 22500
tggctaattt ttttattttt agtagagatg gggtttcgcc gtgttatctg ggatggtctc 22560
gaactcctga ctttgtgatc cgcccgcctc ggcctcccaa agttctggga ttacaggcgt 22620
gagccaccac acctggccta ccctgtgttt attacaaata cacaaattgg ccatttgtgc 22680
gtggctcatc tacagtctca gtgactcaga aggctgaggc aggagaatct cttgaacccg 22740
ggaggcagag gttgcagtga gcagagatcg tgccactgta cttcagcctg ggtgacagag 22800
tgagactgtg tctcaaaata ataataataa tttgttgaat atgtgactgt tggtttaatt 22860
tttattttta tgagatggag tctcactctg ttgcccaggt tggagtacag tggcgtgcag 22920
tggcgcaatc ttagctcact gcaacctccg cctcctgtgt tcaggtgatt cagcctccca 22980
agtacctgag actacagacg tgcactaccg tgcctgacta atttttgtat ttttagtaga 23040
aatggggttt caccatgttg gtcagcctgg tctcaaactc ctattctcaa gtgatccgcc 23100
tacctcgacc ttccaaagtg gcggaattat aggtgtgagc cgtggtgccc ggccagacta 23160
ttggtttggt ttggtgtgat gttatgttat gttatgttat gttatgttat gttatgttat 23220
gttatgttat tttaagacag agtttgtctc ttgtcgccca ggctggagtg cagcggcatg 23280
atctcggctt actgcaacct ccgcctccca ggttcaagtg attctcctgt cttagcctcc 23340
caagtagctg ggattacagg cgcccaccac cgtgcctggc taatttttgt atttttagta 23400
gagacagggt ttcaccatct tggccaggct gttctggaac tcctgacctc atgatccacc 23460
cgccttggcc tcccaaagtg ctgggattac aggcgtgagc cactgcgcct ggctgactat 23520
tggttttatt attaagcagt agtagttgac cctgtcatgt agaaagcatg gcatttatag 23580
gcataccacg tttaatttcc tccccttttt ttatttttgg agtacctcct gcttgtgagg 23640
cttgggaata cagtagtgaa taagccagat gaggtctctc tctttttgga gcttatgtgg 23700
tagtatagac taggcagaaa gttctcattg cccctgccac cttatggcat tgaggtgttt 23760
gagatgctga tgtttacttc tgtctcataa aatcttgaaa ggagttcttt tagatgaaga 23820
ggaaaacaaa atcagaagaa tgggcctggg tcatgtctgt aaacctcccc acgtcatggg 23880
gaggctgaaa tgggaagggc caggagttca agaccaggct gagaaacata acaagacccc 23940
atctctacaa aaaatatttt ttaattaatg ggggatggca gcacacacct gtagtcgcag 24000
ctactacgag gctgaagcga gaggattgct tgagctcagg agttaaagat tgcaggagct 24060
atgatcacag cactgcgctc cagcccctct tatcagcagt ctggtatgtt gctaagggtc 24120
ttgttctttt tagtgcttca gggacagcca ctggctatgc ccagaaataa gtatgtttga 24180
gaagctttct gacctcagct tgaaaaattg attagggtca taattaaaaa gggagggaaa 24240
caggattgag tgaaccggac gctaccgtga gtttattctc ccagggcata cataatctca 24300
tgtgattacc acatagccct gttagataat ctgttatcct gtcctcattt tacccatgag 24360
gaaatgaagg cccagagagg ttaaatgacc tattcaaatt cactcagaag gtggcagaga 24420
tgagttacta tcattgtatt ttggatctct ggaaagaaag aaaactagtg atggtattaa 24480
aaaatgttat taatagtttc ttttaatcaa ccaggaactt gagtcactag cttctctggg 24540
tgaaggacta tacttcaaca gtatgaaaaa cggaaaagaa aatgaggaat tttggctggg 24600
cacagtggct cacacctgta attctagcac tttgggaagc caagggagga gggtcgcttg 24660
agctcaggaa ttcaagatca gcctaggcaa catagtgagg ccccatctct acaaaaataa 24720
attagctggg catggtggtg catgcgtata gtctcagcta cttgggaggc tgactcagga 24780
gggtcactta aacccaggaa ttggaggttg cagtgagcta tgattgcgcc actgtatacc 24840
atcccaggcg acagagtgag accctatccc cccaccgcca aaaaaaagaa aagaaaatga 24900
ggaatttaca tttgtgacag atacggaatt cagggaattt agttgttcat agtctataaa 24960
tgctataaga agtctccata cctttttttt tttttttttt tttttttgga gacagagtct 25020
tgctctgtcg cccaggctgg agtgcagtgg tgcgatcttg gctcactaca agctctgcct 25080
ctcgggttca cgccattctc ctgcctccac ctcccgagta gctgggacta caggtgcccg 25140
ccaccacgcc cggctaattt ttttgtattt ttggtagaga tgaggtttca ctgtgttagc 25200
cacagatccc gacctcatga tctgtctgcc tcagcctccc aaagtgctgg gattgcaggc 25260
ttgaatcacc gcacccggcc ggaagtctcc atacttttta acccaatcta aaatggtaag 25320
gaaatatata agaatgtcta tttattatta aattttttct atataaaaca tttcagaaaa 25380
taaagactag catttctgag ccaagtggta gtagtggcca ttttttctgg aaaaaaaaaa 25440
aaaaagaaag aaaaaacaca tttagctatc tatgatgtga aaagatgaac attttattta 25500
ggtaataaat gttatgtcat aaaataccat ttattgtgtg cctattaggt ttcaggagag 25560
ctgtgccaag agcattactt gtatatcttt taagccttac aacagcccag cctgtcaggc 25620
tggtagtgcc atatctgttt tacagatgag gaagtgatgg attggagaaa ttaaggaaat 25680
tgcctttagg tcaaagagat aggaagtgac aaagctgaga tttttaacct tgtgagattt 25740
caaagtcttt gctttttaat aactgttcca ttgcttctaa tatagagata tgacaaaaac 25800
aagtaaaaat cagtgaagaa ggctgggagc agtcgcttat gcctgtaatc ccagcagttt 25860
gggaggccga ggcgtgtgga tcgcctgagg tcaggaattt gagaccagcc tggccaacat 25920
gacaaaactc cgtctctact aaaaatacaa aaaagttagc caggcgtggt gacaagcacc 25980
tgtaatccca gctactcagt aggctgaggc aaggagaatc gcttgaacct gggaggtgga 26040
ggttgcagtg agctgagatc gctccattgc actccagcgt aggcaacaaa gcaagactcc 26100
gtctcaaaaa ataaataaat aaataaataa aaataataac aataatgaag aaaacaatcc 26160
ggtgattatt gtcagcaata aaatttcttc aatcaaccat gctttagtcc tggcagttct 26220
ctatcagtga gtttcaatca aaaagtttgt ttataatttt ttttttttta aaattttgaa 26280
atttggaaac aacatcataa atgatggtta gttttctgca gctccctatt ttggcagata 26340
gtctgttgtt actcataatt aatttgaact aaaaagtagt gttgtacgat atcatgggct 26400
gtgaatgtgt ttgtgacttg atctgagaac ccacacacca cttaggatgc ttctgtagga 26460
aaattagagt atggaactca cttgcccacg ctttccctgt ctcagtccat gttggtaggc 26520
tgcaaagtct ggggctagaa ggacactgaa caagacttca gcagtacatg ttagtcttcc 26580
agagggaagg aatataatag ttgagagaat aattcctttc ctctgtgact ttaggcaaat 26640
tcttggctat gctgttattt atttgggcca aacaatatca ggaggttgta cattttattc 26700
ttaattactg cgatacatta attttatcca tgggtttaac ctagcctacc ttttgctgtt 26760
agacttcaac tctacttgtg ttgggttacc cctctgctta aaaatcaccc tattcccaag 26820
cctgagggag tctaccttca aagctttcta tgacctaatc caaggcctgt caaacttcgt 26880
aaagggccag atagtaaatt tgtttttttt ttttgagatg gagttttgct cttgtcaccc 26940
aggctggagt gcaatggtgc catcttggct cactgcaacc tctgcctccc aggttcaagt 27000
gattctcctg cctcagcctc tcaagtagct ggggttatag gcatgtgcca ccacgctcgg 27060
ctaatttctt tgtatttagt agagatgggg gtttcaccat tttggtcagg ctggtctcga 27120
actcctgacc tcaggtgatc cacctgctgc ggcctcccaa agtgctggga ttaccagtgt 27180
gaaccaccgt gcccagcccg atagtaaata ttttaggctt tgcagtccat atacagtccc 27240
atttttttgt gtatgtttgc acgttttctt tacatatttt aaaagcccct tttttttttt 27300
ttttgagaca gagtcttgct gtgttgctca ggctggagtg cagtggtgca atcttggctc 27360
actgcaacct ctgcctcctg ggttcaggcg attctcctgt ctcagcttcc cgagtaactg 27420
ggattacagg cacatgctgc cacgcccagc taatttttgt atttttagta aagatggggt 27480
ttcgccacat tggccaggct ggtctcctga tctcaggtga tctgcccacc tctgcctccc 27540
aaagtgctgg gattacaggt gtgagccacc gtgcctgacc taaaagctct ttacagtgta 27600
aaaaatattc tgagctttaa gccatgtgaa aataggccat gggcatttgc tgacccctaa 27660
tagaactcca ttttaccttt ctgatcatgt ttcccattaa ctcttcaaaa atatgacctc 27720
catttaaatc aagatggtct ccttcctcac tgcttgtgga ggtccagtgc ccagtgtctg 27780
cctcttgctt gctcctccat cattgttctg ccattcgaga tcctcatact taccctttaa 27840
gatctagccc aaattttcca tgaaactaat tctaataatt aaaaacttcc tgtagaactt 27900
aactttgtct agtacaagtt agctttctta ttcagtagta gcttactata aattacaaga 27960
ataaaaagat taccattttc cctcacactg ttttgtggag aatgcctaaa gttacttttt 28020
ctttttacag gtcagtattc ctatttggca tcctaatccc ctttcccaaa tctgaatttt 28080
gggatttgaa gcttgcattt gagattatga tttgtcttcc ttgttgtaca caggagcagg 28140
gactttacaa ttagtattcg catccctgct ccttcatact tcgtgatgta aggcaagtta 28200
ttttcactta tgcttaagtt tcttcccctg taaaaagggg atggaagagg attaaatgaa 28260
ttaaacatgt aacacgctta aagcaatgcc tggcaagtaa taagtgctca gtaactttta 28320
gctgttctta ttagcatgtt tggaaaccag tagaaactac accagcaagt taaggttgaa 28380
aagtggtatt gatgggcttg gggtagtaca gtatgaatgg ctacagttta gcgtttcatt 28440
aagtttgtat attcattaat tcattacaca tttgatgctg tcagactagg acagagacaa 28500
agatgaatga aacattatct ctgcttccag gttacccagt gtagtagaga aggcaggcat 28560
gcagatagtt taaattggta gcactgggag gggactgcca tgggtgggca gtgaagaaaa 28620
agggcttcaa aataatgaga gttgagatgg atcttcaagg aagataagca gttttcagta 28680
aggccatgaa gagaggagga agttccaggc gggaagagtt tgtgctaaag tacagggatt 28740
gctatacaca tggtgtatgt agaaaaaatt tggttcacag tgtgatagaa gaattggagg 28800
gggtcctcac tgaaagtaag gaaacacatt tggaagaata tgtttcagtt agaaaatgaa 28860
atgagcttaa agtaaacgct aataaggttt ttaaaatgta aaatttcaac gtatttagaa 28920
agagaacagc tggatgaatc ttatgtacct gtcactcagc tttagcagtt atcagtaaat 28980
ggccaacgtt gtttcagcta tactcccctc tcctccactg atagtctttt gaaggggaat 29040
acaattgttt tgtggcctcc agaaagggat aagtttatga gcaacgggta gatcgttggg 29100
agagacttga gtttcctgtc aggaagcatt cttggtgcat aagtcagagg tgatatgaat 29160
gccgtggaag ggggtggctt actgtctgga gaactcgaga agatgggaat gggcactgtc 29220
cagtattgtg gctacttcca cacatggttc tttaaattta aaattatgtt gattaaaatt 29280
taaatatttc agttcctcag ccatactaat cgtatttcaa gtgcttagct gccacatgtg 29340
cctaatggct gcaatattgg acagcatgac ataggacatc ttcatcattg tacaaagttc 29400
tcttggacag catgggacta gagccctaag atccttttct acctgagttg tttggatttt 29460
ttggtgtgtc taggttggat ctagttgttc atggcttcat gaccaagcct tttatccctt 29520
tctctagagg gactcaaggg gtaaaggcac tgaaggggta aaacttcata tgaagagtgt 29580
ggtggtggtg gtggtgtttt aagacagggt ctcgctctgt cactcaggct ggagtccagt 29640
ggcatgatcc tggctcactg cagcctcgac ttcctgggct taagtgatcc tcccacctca 29700
gctcccaagt aactggaact gtaggcatga gccaccacac ctgcctaatt tttaaaactt 29760
tctgtagaga cgagatttcg ccatgttgtc caggctggtc tcaaattcct ggactcacct 29820
tggcctccca gagtgctggg attgcaggtg tgggccactg cgactggcct tttttttctc 29880
ctttactact ctagtgtatg ctggaatatg aggaaataat tatattagct agcagttatt 29940
aaacacttaa taacatacca ggcactgttt taagctatgc gatctgtatg gaatattact 30000
taatttccac aaccttatga aaagatacta ttttttttct tttgagaagg tactattttc 30060
atcttcattt catagatgtt gaaattgaaa cacagagagc tgaagtcaca ggattaaggc 30120
cacagagctg agaagtgatg gagccggaat ttgaacccaa gcaattaatg ctgatattag 30180
ttcttgtgtg aatggtaatt gttttgaaac aatgatccta gatgattata tgaccggatt 30240
aatctggcag ttgttctgtg tgaatttaga gttgccttcc cacctcagtt tcctaaaaac 30300
aaaacaaaac aaaacaaaac aaaaaaaact ctagcttcac tgtgtttggg ttgtcatggc 30360
ctaccccctc ttgccacctc atttgactca actttttagg gagaaaatat tcaatacgtg 30420
gtataggatt tccctttcta ataataatgt aaacaacaac aagaagtctg aaattggaag 30480
aacaaaatga ctcacctaag tgagttaacc ttaagaggtg gaacttgatt tctagatttt 30540
agttaattgt ctaactgatg tactaaatat tagttactta agtattaaaa cgggtagaca 30600
taatagttgg ggagctgctg tagagggggt agtttgagaa ggcttctttc aggaggtgac 30660
atttaagttg gtaactaaca agaaaggggc agccatgtga atagctggag ggaagagcat 30720
tcttacagtt ttactggaag ggggttagag gtatgtggta cccttatgcc aaagaaaatt 30780
agttacttct atacaaccag tctgattcta gaaacctgga tcaatgaaat attttgatta 30840
tataaaaaaa tctgttaccc aggtcttgtt gaaatagcat tagaaactac tgaaggacat 30900
atagaggagg agtgttgaaa aatggtgatg gatgagcaga atggtgaaaa ataaaaagac 30960
atgaagctct ataattatat tgtatggtga cagtaccaat agagattgca tgttttttct 31020
ccccagtttt tttttttgtt ttgttttttg tttttgagac agagtctcac tgtgtcactc 31080
aggctggagt gcattgtcgt gatattggct tactgcaacc tctgcttcct gggttcaagc 31140
gattctcctg cctcagcctc ctgagtagct gggattacag gcatgtgcca ccacgcccgg 31200
ctaatttttg tatttttatt tgagagggga tttcaccatg ttggcaaggc tggtcttgag 31260
ttcctgacct cagataatcc acctgcctca gcctcccaaa gtgccgggat tacaggtgtg 31320
agccactgcg cccggcctcc cccagttgtt gaaacaataa tggaaggtaa ttttattctt 31380
agattattta atgtttttca gttatcagga tgtgttagat tgtttgtgta tattgttttg 31440
cttgttaatt aagtaacaca gtgaataaga cagacaaaca tacgaaaatg tacatttatt 31500
ttattttttt gagacagtct gttgcccagg ctggagtgca gtggcccaat ctcggcccac 31560
tgcaacctct gcctcctgag ttgaagcgat tctcttgtgt cagcctcatg agtagctggg 31620
gccatgggtg cacgccacca tacccggcta atttttatat ttttagtaga gatggggttt 31680
caccatattg gccaggctgg tctcgaattc ctgacctcag gtgatctgcc cgccttggtc 31740
tcccaaagtg ctgggactac aggcatgagc cactgtgcca ggccatttca tttttggaac 31800
gttctttttt ttttttgaaa tggggtctcg ctctgtctcc caggctggag tgcagtggct 31860
caatctcagc ttactgcaac ctctgccttc cgggttcaag tgattctcct gcctcagcct 31920
cctgagtatc tgggactaca ggtgcatgcc accacgccag gctaattttt gtatttttag 31980
tagagacggg gtttcaccat attggtgagg ctggtcttga actcctggct tcgtgatctg 32040
cccgcctcaa cttcgcaaag tgctgggatt acaagtgtga gccaccacgc ccggcctgtt 32100
tctggaatat tcataatctt ttgttgtcat ttcaacagtg ctcacagcag cttcaccagg 32160
tgtagattcc atcttaagaa accactttct ttgcttatcc atgagaagca acacctcatc 32220
tattcaagtt ttatcatgag attgcagcaa ttcagttaca tcttctgacc ccacttctaa 32280
ttttagttct cttgcttttt taccacatct gcagttactt gctctactga agtcctgaac 32340
ccctcaaaat cattcatgag tattagaagc aatttcctgg ttgggcacgg tggctcatgc 32400
ctgtaatccc agtactttgg gaggccaagg agggcggatc acctgaagtc aggagttcaa 32460
gaccagtctg gcaaacgtgg tgaaaccccg tttctactaa aaatacaaaa attagcgggg 32520
atgtggtggc gggcgcctat aatcccagct acttgggaga ctgaggcagg agaatcgctt 32580
gaacctggga ggtggaggtt gcagtgagtt gagattgtgc ccttgcactc cagcctgggc 32640
aacaggagcg aaactctatc ttaaaaaaaa aaaaaaagaa aagcaatttc ctctaaaact 32700
cctgttaatg ttgatgtttt aacctcctcc catgctcatg gatggcattc tcagtggcat 32760
ctagaatggt gaatactttt tagaaagttt tcaatttatt ttgccatcag agaatggcta 32820
tgaatggcag tagtagcctt acagaatgta tttctttttt tttttttctt tttttttgag 32880
atggagtttt ttttgctctt gtcacccagg ctggagtgca gtggcatgct atctcggctc 32940
accgcaacct ccgcctcccg ggttcaagca attctcctgc ctcagcctcc tgagtagctg 33000
ggattacagg catgcaccac catgcccacc taattttgta tttttagtag aggcggggtt 33060
tctccatgtt ggtcaggctg gtcttgaact cccgatctca ggtgatctgc ctgcctcggc 33120
cttccgaagt gttgagatta caggcgtgag ccaccgcgcc cggccgtatt tcttaaataa 33180
aatggcttaa acgtcaaaat tatcccttga tccctgggct atggactgat tcttgtgtta 33240
gcagttatga aaacatttat gtccttgtac attcccatca tagctttttg tcaatgagaa 33300
gtaatttttt tttttttttt gagacagaat ctcactctgt ttcccagcgt ggagtgcagt 33360
ggcatgatct cagctcagtg catcctacaa ctctgaggtt caagcaattc tcgtgcctca 33420
gcttactgag tagctgggat tacaggcgcc caccaccacg tctggctaat ttttgtattt 33480
ttagtagaga tggggtttca cgatgttggc caggctgggc tcgaactcct ggcttcaagt 33540
gatccacctg ccttggcctc ccaaagtgct gggattgtag gtgtgagcca ctatgcctgg 33600
cctaattggc ctaatttcaa tattgttata tctcagggaa tagagaggca cgaggagaaa 33660
gagagacaag ctgactgctg gttcgtggag tagtcataac acacaacatt tattaagatt 33720
gctgtcttat atggaccgtt tgtggtgcct taaaagaaat cagggtaaca tcaacgatta 33780
ctgattacag attactataa cagatacaat aataattgta aattattatt tacaattgta 33840
aaatacaatc ttttctttat tatttacaat tattgtaaaa tacaatctga ttacagatta 33900
ctataacgta tacaataata gtggaaaagt ttgaaaatat tgtgagattt atgagaatgt 33960
gacacaggcg caaagagagc acatgttact ggaaatacgg cactaatgga cttgcccgac 34020
tcggggtttc cacagacggt cagcttgtca aaaatgcagc atctgtgaat ttcaataaag 34080
caaagcagaa taaaatgagg tatgcatgta ttgccatcac atgtacacta gtaaaatacg 34140
tttttttttt cagtaggtgg atcaacctca aattttaata taaagcatta cttaaaggag 34200
aatatgggga cattcatgac atttcttata tgtacataaa acttcatgaa aataatttaa 34260
tgctatccag cagtttattt tagaagtact ggaggctagg catggtgtct tatgcctgta 34320
atcccagcac tttgggaggc tgaggtagga ggatcacttg agttcaggag ctggagacca 34380
gcttgggcaa tatagtgcga ccccatctct acaaaagaga aaagaagtac tggagtgttg 34440
cagctcttac agaatttgtc tagcaggttt tccagtcttt accagaaatg cccccatgca 34500
gaagtagtaa atactgattc atgtaaaata ataaacaact ttatctttca gtttttaaaa 34560
gacagggtct tgtaacgttg cccagactgg cctttaattc ctgggctcaa gcgatcctct 34620
cacctgagcc ttttgagtag ctgagactac aggctgcacc tctgcacctg gctctgcttg 34680
atttttaatt gttgtattgc tgttgcagct atgttttttt ttttcttcag tgtgaggatg 34740
ggcaaacttt ttatgtaaag tctcaggtaa taagtatttt aggctctagg gccatatagc 34800
ttctctgttg catatccttt tttttttttt ccatttcccc tcaaattcct tttaccataa 34860
gcaactcttg aggaacataa aaatcattct tagcccagaa gccagaccaa aacaggttgt 34920
gggctgtagt gtcctgaccc ctgatttaaa gattgatagc tttgaaatgg aaagttttaa 34980
ctttcttttt ttttctttcc cttgttctga ttgggctgtt aattcattag gtatttactc 35040
agtgtgtatc atatgaggca tgattcctct gctaattttg gtagtggtag aaagatactt 35100
ttgccaagct tggttgttag gttttcattt gtccaagagt tcctgaccaa gtgtgaatgg 35160
atgttgaaat caaggtgttt ctttggccac acaatgtgcc tttgggggct atatctatgt 35220
gcttctggta ccttctttta attttcacaa agacactgct tgccgaccac actgttttgt 35280
ctaatgtggg gctatgaccc cctggaagag gcatcatttt ctgattttca cagaagcata 35340
atatggtcag gtgatggtcc tgagtagtgg gtatatgaca gatacactag taattataat 35400
acagatctaa actggagagt tgaaaacagc atcgtatatt tgattgagat aatcgaagga 35460
agacttcctg aaaagatggc atttgagttt caaggctgag taggattaag tattattatt 35520
taaaaaatgc cttggacaat gcattaaata gagttaacaa atcacatcac ttatagtctc 35580
caattaaaaa cattttactt aaacataatt ttagactttt agaaaaattg caaagatatt 35640
ataaagaatt ctcctatata tctcacctgt attcttcaag taacatttta ccatattcac 35700
cttaacattt tctctgtatt ggtaattgta tatgtaagat ttaatataaa ataaaaattc 35760
ttattaaaca tatgagagac atgatgcctc tttagcccta aatacttcaa cttgtatgta 35820
ctaataacaa gggcattcta tttcaaaacc acagtacagt tgtcaaaata aggaaattaa 35880
taattgtgtc aaactgttat tctgtttata gaccttctaa tgtcctttaa aacaatcaac 35940
aaatcaacat ttttctggtc aagaaccagt aaatatgtat attctacata tatatataca 36000
catatatata cacacatata ttctacatat atatgtggaa tatacgtatt tactccctct 36060
gtccaagaac caatccagga ttgttacctt cggttatcat gtatctttgg tctcctttaa 36120
tccaaagcag tttctttgtc ttttatgact tgacactttt gaagattaca ggttattttg 36180
tagactgtcc ctcaactagg gtttatctga ggtttcctta tgattagatt cagatattta 36240
tttttggcag gaatacaaca gaaatgattt gtgtgttttt ctcattgcat gatatcagaa 36300
agtgcattgt atatatttat cccattactg gggttgttaa ctttgatcac ttggttagag 36360
ttgtgtctac taagtttctt cactataaag ttatttttca cttggtcatt tcatcagtat 36420
cttgtgggga gttactttgt ggttatataa atactctgtt tctactttcc cttactatat 36480
ttagcttctg tggacacttt tgcctgaaac agttatttac tatggtgtta ccaagtagtg 36540
atgccctttt cttccatcat tctgtctaca tttttttttt tttttttttt tttttgagat 36600
ggagtttcgc tcttattgcc caggctggag tgcggtggcc tgatcttggc tcactgcaac 36660
ctctgcctcc cgggttcaag cagttctcct gcgtcagcct cccgagtagc tgggattaca 36720
gacatgcgcc accactcctg gctaattttg tatgttcagt agagacagga tttttccatg 36780
ttggtcaggc tggtctccaa ctcccgacct caggtgatcc acccacctca gcctcccaga 36840
gtgctaggat tacaggcgtg agctgccaca ccaggccttc tttttctctt ttaagagata 36900
gagtcctgct ttgtcaccaa ggctggagtg cagtggcatg atgatagttc actgcagcct 36960
caaactcctg ggctcaagtg aacctcccat ctgtagctgg gactacaggc acctgcataa 37020
cacctgactg ttttttaaaa ctattttaga gatggggtct tgcgaagttg ctcaggatgg 37080
tcttgaactc cgggtcttaa gtggtccttc tgcctcagcc tctggattag ttggcattac 37140
aggcatgagc cattgtacct ggcaagtgca tattttcttt tttttttttt aaggtggagt 37200
ctcgaggccg ggcgcagtgg ctcacacctg taatcccagc actttggaag gccgaggtgg 37260
gtggatcaag aggtcaggag atcgagacca tcctggctaa catggtgaaa ccctgtctct 37320
actaaaaata caaaaaatta actgggcatg gtggcacacg cctgtagtcc cagctactcg 37380
ggaggctgag gcaggagaat tgcttgaacc caggaggtgg aggttgcagt gagtcaagat 37440
catgccactg cactccagcc tgagcgacag aggtagactc tgtctcaaaa aaaacagaaa 37500
gacggagtct tgctctgtca cccaggctgc attgcagtgg catgaactcc gcctcctgag 37560
ttcaagcaat tcttgtgcct cagcctccca agtagctggg attacagaca tgtgccacca 37620
cacgtggcta atttttatag ttttagtaga ggtggagttt caccatgttg gctaggctgg 37680
tcttgaactc ctgacttcag gtgatccacc cgccttggcc tcttgaagtg gtgggattat 37740
gagtgtgagc cactgtgccc agccaagtga gtatttgctt atgtagtatt ttaattttat 37800
gatttttttt tctttgagac ggaggtttgc tcttgttgcc caagctggag tacagtggtg 37860
ccatctcggc tcactgcagc ctccacctcc tgggttcaag ccgttctcct ccctcagcca 37920
cctcctcctg aatagttggg attataggcg cctgccacca tgcctggcta attttttgta 37980
tatctagtag tgatggagtt tgagcatgtt gccaggctgg tcttgaacct ctgacctcag 38040
gtgatccacc tgccttggcc tcccaaagtg ctgggattaa ggcatgagcc accatgcccg 38100
gccagagact gttcatttat tttttttttt tgaggcggag tctcgctgta ttgcccaggc 38160
tggagtgcag tggcacaatc tcggctcact gcaagctccg cctcccaagt tcacaccatt 38220
gtcctgcctt agcctcctga gtagctggga ctacaggtgc ctgccaccac gcctggctaa 38280
ttttgttttt gtatttttag tagagatggg gtttcagccc gccttggcct cctggagtgc 38340
tgggattaca ggcgtgagtc agggcgcctg gccaatcata ccttctttta ctgcattaat 38400
tatggttttc tttcgttctt aaaacatgtt tatagtgacc acttttgaaa ttcttattaa 38460
gtcagacatc tggttataca agcaatttct attgcctact tctttttcca gtgggtgggg 38520
ttatactttc ctgtgtctta gcttgtcgtt tttttttttg ttgttgaaaa ctggacattt 38580
taagtaatgt agtaactctg gatacctcat tagcctatgg ttgggggtgg tggttgttac 38640
tgttatttgc ttatttgtct aatgactggc tgaatgattt tagtgttcta tccttcttcc 38700
ctccctgtac agtgtgacac gtctgatgct agttttcttg ggatgcagcc ttgggtatgc 38760
ctaccatcac tctagaatca cagtgatttt ggcatggctt tgtctctttt cctgactgta 38820
cccagctgtt aagctacact aattactagg tgatgctgtg tagtcatttc ttggtgtcct 38880
tgggggattg gtcccaggac ccccccgttg gatataaaaa tttatggatg ctctagtccc 38940
tcataaaatg gcacagtatt tgcatatacc ggtgcacatc ctcctgtatg ctttgtcatt 39000
tctagattac ttataatacc taatatggtg taaacactag gtaaatagtt gttatatatt 39060
ttttatttgt cttattttta ttgtatttat ttttaagtgt ttttaatctc gagtgattga 39120
atctgaggat gtgaaatctg cagatatgga gggcctgcat tgttttccgt ggagctttgg 39180
gcctaaactg ctccacagac tgatctgatc aaatttgcgc ttctttgaag ggatagtttc 39240
tgagatcagt gtttgaaatt tgttccaatc cacagaggag tcctcccagc tctctttccc 39300
tagttctggc caccaaacta gacaactaca atttagcact tatctccaat gattctcctc 39360
ctaccaagtg cctttgaaag catcattaac tctttcatac cttgttgcaa atgaaatttc 39420
tttgggaaga gattgtgagt tttttttctc ctaaattatg gtgcaatata agtaatatac 39480
cattttaaca attttaagtg tattaagtgt tttttttttt tgtagttttt ttttttttgt 39540
tttttgagat agtcttgctc tgtcgcccag gctggagtgc agtggcacga tctcggctca 39600
ctggaacctc cacttcccgg gttcaagtga ttctctggtc tcagcctccc caaatatctg 39660
ggattacagg tgtgcaccac cacgcctggc taatttttct atttttagta gaaacggggt 39720
ttcaccatat tggtcaggct ggtcttgaac ttctgagctc gtgatccacc cacctcggcc 39780
tcccaaagtg ctgggattac aggccttagc caccacacct ggcctatgca ttgcttttat 39840
atgtatttta aaattcataa gttctcctcc tatgatgttt ttgtcccatg tgatttattt 39900
gttaaaccgt catctttggc cgggcgtggt agctcacgcc tgtaatccca gcactttggg 39960
aggctgaggt gggtggatca caaggttaag agatcaagac catcctggcc aacatggtga 40020
aaccccgtct ctactaagaa tacaaaaatt atctgggcat ggtgacgcgt acctgtagtc 40080
ctagctacct gggaggcgga ggttgcagtg agccaagatc gtgccactgc actccagcct 40140
ggcgacagag tgagactctg tctcagaaaa aaaaaaaaac aaaaaactgt cattttttat 40200
gttgcattta ctgcattctg gatttaaact gtgaggaacc tcatggtatc agttaatata 40260
ttcttccatc ttaatgtttc tcgtaaactg gtagatctgt aaacttgatt aggtctatcc 40320
tattgtatca catcagaagc agaaggtgct tttttttttt tttaagggaa attgtgtgaa 40380
agtagacaga atggtaaagt gaacccctgc acacctatca cccagcttta atagttatca 40440
gctcatacca ttcttgtttg atttacaacc ccattcattt ctcccttctg tattattatt 40500
atttagttaa ttattttttg agacagggtt ttgctctgtc accaatgctg gagtgcagtg 40560
gcataatcac agctcactgc tgtcttgacc tcctgggctc aagtgatcct cccacctcac 40620
cctaccaagt agcggggacc acaggcgtgt gccaccatgc ctggctagtt ttttattttt 40680
tgtagaaaca gggttttgct ttgttgccca gactgatctc aaactccggc actcaagtga 40740
tcctcctgcc tcagcctcct aaagtgctgg gattacaagc atgagctacc acattcagca 40800
tgtaaatttc tttatattaa tttgactggc attttaagtc acacttgaat ttcatatttg 40860
gcaactatta aaagcataga gtcctggata ttagtgtttt gttaaacctg atctatctaa 40920
tcataaatat acttaggtct aaaatatgct cttggccttt gtttattgcg gttcagtatt 40980
tgttactata ttaaatagta aaatatttgg tttgagatac taatgaaaag attaaaagta 41040
aagcataact tgaatggata caaaaagaaa caagaattta gacttcagtg gatttcagag 41100
aatactgctt cgatatgcta acattcctgt tgggtgtcca accgtgtcat agatcagtgg 41160
aaattagtgg tttctgcact ttactgtact gtttttttat atgataatat tttcctggtt 41220
gaatgattcg ttcttttgag taaactccat ggtcaaacaa ttacttttta ttagtcaaag 41280
atgtaaccac ataatcacta aaaagaacag tgtgacttat ttaaagggga ttatgttttt 41340
aagtctttta tatagctttg tagggaggcc atatgagttt aaggacagtt cgtggcattt 41400
gttcaaggtt ttgtaacttg gcatctcagc agccaccagg ataccagatc atcgttctaa 41460
gtaagattta ggcattttag ccttcatgta cagactataa gtacaccccc ccacacccct 41520
accaaaactg taaattcaaa tgatgtttga aaaagcatag aatttttgtt aggcgaggta 41580
gtttattcct tgtgatacag ttccagagag gcagcataac ctaggaatga aaaacttaga 41640
cgtggaatca gatacacctg gtttaaatac cagctctact gctcatgaac tggatgattt 41700
tggtcaagat acttgactgc tgaggttcag tttcctcacc tgtaaagtag aggtgataga 41760
ttagacatgt tgcatgtgaa gtacttagta tggtgtctgg ttttgtagta agatctataa 41820
aagataaatt attagtcata ttccttagac ttcaggaatt tatctctgtg ccatgtttga 41880
ggcaaacagt tacagaatta gaatgttaga aatgaaagga atcctagatg tcatttaatt 41940
caagtccatt gttttctgga tgagagaaga aagtgaggaa aagtgacaga gttggagacc 42000
aagctaggac tggcctcaga atgttaagag tactcttcta gggatcgacc agtcgtgtta 42060
ctagactttt tggatctgaa ttgtgctttt ccttgaatgt tttgaatttt ggcttgagtg 42120
ttgtgattat tttattaaaa tgagattcca gtcctattgt catgactaat gtttatgaga 42180
aatataacat ttcactttaa tgatgttttt taattattct aaggggccta atctttttca 42240
gtggaataag ctttaggttg tattatattc tataattcac ttgaaaatag aattcatctt 42300
tacttgacag ccaaattttg tgtactgcat cttttctgag ggagagagtt ggcaaggaaa 42360
ggcacttgtt acaacgatcc acacatatag acgcatatta tttagaaatg aaagtgcttt 42420
gaatgattta gcttattttc agtttttttt tttctgcagt tgtaatcata tgacctgttt 42480
ttctttcttt tttttttttt gagacagagt cttgctctgt caccccggct ggagtacaat 42540
ggggcggtct cagctcactg caacctccac ctcccaggtt caggcgattc ttctgcctca 42600
gcctccctag tagctgggac tacaggcgca tgccaccaca cctggctaat ttttttattc 42660
ttagtagaga tggggtttca ctgtgttagc caggatggtc tcgaactcct gaccttgtga 42720
tctgcccacc tctgcctccc aaagtgctgg gattacaggc atgagccact gcgcccggcc 42780
catatgacct gtttttcttt tatagatggg ggagaaatat gggaagtgac ttggtgtcag 42840
tcatctgtgt tggttaaatc aagaatataa tccgtgtttt gcttctgaat agctctttat 42900
aacagtgatt ggttactttg ggagtaaaga ttattattta gagacagagt cttgctttgt 42960
cgcccaggct agactgcagt ggaatgatcg tagcctactg cagcctcaga ctcctggact 43020
ctggtgatcc tgcctcagcc tcctgagtag ctaggactag aggtgcatgc cacatgcctg 43080
gctataatta ttattaattt acgtttagca ttagtttttt tcttccagta ggctatttta 43140
ctttatttat ttgattttga tgaagtttga ttatttctag tttgcttcct tctatgaccc 43200
ctacctgttg tgggtctcca ggcaagcagt gcataggtag agccatcctt aggtagcctt 43260
tagacttaat attaggtgag ctctccccac agatagcctc tcctttattt gaatggaatt 43320
atattttaag tttggaaata tttttcagct tatttagcct gttgaattta ataaaaataa 43380
tatttaatct tttcagaggt cgaaacagta acaaaggact gcctcagtct acggtgagta 43440
actttaatgt tacttattgg ggaaaattag tagctaaaac atgatctcta accacagacc 43500
aaatgccaag gcaaaagatt cccttctttt gaattttgtc atagataact tgactgttta 43560
agtatgttat tagcctatat gtgttttttt aatgactctg tataaaatgt acaattactt 43620
gttgtattag tccattctta cactgctaat aaagatatac ctaagactgg gtaatttata 43680
aaggaaagag gtttaattga ctcatgctct gcattgctgg ggaggcctca ggaaacttac 43740
aatcatggtg gaaggggaag caaacacatc cttcttcaca tagcgacagg agagagaagt 43800
gctgagcaaa gcagggaaag ccccttataa aaccatcaga tctcctgaga actcactcac 43860
tatcatgaga gcagcgtagg ggaaactgcc cccatgattc agttatctcc acctggtctt 43920
gcccttgaca cacgagaatt attataatta aagataagat ttgggtgggg acacagaacc 43980
aaaccatatc atttgtaaat agtatttttg tcacgtgtaa taacaagaac aagtcgcttg 44040
ttcttttcta aatgactaag tgcaaatcta agtgaaaaac ctccaaaaga tacgtagaac 44100
accaagagtg gagtctgcag agttctttat gctttttatt ttgaattaat gtgctttttt 44160
tctgctgctt tcatttttct cctttggctt tctggtctta aattttggaa tgttatcaat 44220
gaaattgaac cggacatgaa gggcagaaac tataagtccc acatgatgga agaaataaat 44280
gagaagctat cacaaatttt tgagactttg cctttattag attgttttac aagaatcagg 44340
aagatataca cgtatatggt agtaatatgg agtagtgtgg ttgatcagac ttaagcactg 44400
tcactgatgc tgatatgctg ggagaaccta gtcagggttc ttctatgaag gtatgacctg 44460
gcttcctacc ccatttattt atacttcacc cttcttaggg tacatttctg tgagttttaa 44520
caattgcata caatcagtgt aactaccacc acaatcaagt taatagaaca gtttcattgc 44580
ccaccaaaat ccctcaaatc acttttcagt gaaccctcct ctctctccaa ccattgattt 44640
gtcttccatc cttacggttt gtgtccttcc tcctctatgg aagtttactc ttgctttttt 44700
atgtcatgtt tagtcaaaac accattagtt ggtttgactg ataacacttg aaaacctgac 44760
cttctgttcc ttctgttctc tatggaagca aaatattaaa taaacaaaat cttcccttaa 44820
tacatgtaag atatcataaa cctaactaaa cattttgcaa caaataataa acgttagctt 44880
tatatgcaaa tgtaaataca ggctgagcat ccctaatcgg aaatgctcca aaatttcata 44940
ttttgaatta gggatgttca agcactaagt ataatgcaaa tatccccaaa tccgaaaaaa 45000
atccgcagtc taaaatactt ctggtcccaa gcattttaga tgaggaagat tcagtttgta 45060
ctaatttcta atagtttttt ttttttttaa tattccagat ttcttttgat ggaatctatg 45120
caaatatgag gatggttcat atacttacat cagttgttgt aagttattag attattgggg 45180
ataaactgcc ttgggggtag aataaagtaa ttccatgaag ttaaaatgtg gataaatgat 45240
tgtcaaagta acattgctta gatcatgttt agtcaggatg atttagagaa atagattaga 45300
actcctttta tccagtctaa tataattcat tgtaaaagta cagttggtcc tctgcatctg 45360
tgggttccat attcatggat tcagccaacc ttggatcaaa aatatttgtt aaaaaggcca 45420
ggcacagtga ctcacgcctg taatcccagc actttgggag tttgaggtgg gcagatggct 45480
tgagctcaca agtttaagac cagcctgggc aacatggcag aactccgtct ctacaaaaag 45540
taaaaaaact agccgaacgt ggtggtacgt gcctgtagtc ctagtgactt gggaggctga 45600
cgtgggagga ttgtttgagc ctgggaggtg gaggtttcac tgagctgaga taatgcccct 45660
gcactcagcc tggtcaacag tgccagacag accccttctc aaaaaaaaaa attttttttt 45720
tttttttttt tttttttttt tttgagaaaa aagaggcatg gttgcgtctg aaccaaagat 45780
gtacggacgt ttttcttgtc attattccta aaacaataca gtatgacaat ttacatagca 45840
tttacattat attaggtatt acaagtaatt tagggatagt ttaaagtatt tgggagaatg 45900
tgcttagtta tatgcaaata ctattacatt ttatgtaagt gacttaagta ttatgtaatt 45960
cggtatctga aggaggtcct ggaaccagtc ccctaccaat aacaacagat agctgtattc 46020
ttgttaaccc tgctgtgtgt gtaaaataat gttagtagtt gattgtcttt tgtacattat 46080
tttgtcactt aaaatagctg gggtcagaaa tgtttgactt cagtattaaa attcgtactg 46140
caaactctga gtagagcctc ctgaagaatt tcaagagttc agtgtattgt taatgttttg 46200
aaattttttt attgttttgt tagtgaatac ctaatattga atgaagcctg atgaggtata 46260
aaaagtaaaa tgaaaacaaa tatccctggt gaccgggtag tatactgttt ctttgataaa 46320
taaattatat gtttttaggg ctccaaatgt gaagtacaag tgaaaaatgg aggtatatat 46380
gaaggagttt ttaaaactta cagtccgaag gtaattttta ctttttttct ttttcttaca 46440
aagtaaaaga acattttcat agtcagtgtt ttacctagtt tttaaagcca ctttgaatga 46500
ttttacttct cagtttcaaa tactgattat tttatagact ggtttgtgta atcagagagg 46560
cttcttgatg tgtgtgctta ttaaaatatt tcaaccattt ttaagcattg tgagctaata 46620
gagggatgtg gtggtttgtt ttttcctctt aaaaattatt attaatgtac ttaagacaaa 46680
ccatagaaac aaaaaacatt tagatatgag gatttttaaa tgatggaatg gataatagat 46740
catatgcctg ggaaaaaggg tatgattctc ttgagattat ttttgtcaaa ggcatataag 46800
aactggtacc ttgatgagct aaagaattcc taacaaattt tattttgtaa aggtttggag 46860
tacttacttg tgtttttcat tttagtgtga tttggtactt gatgccgcac atgagaaaag 46920
tacagaatcc agttcggggc cgaaacgtga agaaataatg gagagtattt tgttcaaatg 46980
ttcagacttt gttgtggtac agtttaaaga tatggactcc agttatgcaa aaagaggtgg 47040
gttttgattt cctaaatatg cctcatggtt tattagattt attcaagcaa agattttcac 47100
agtgatctta caaacttttt ttaaagaaat atctgggctg ggtatggcgg ctcattcctg 47160
taatcttagc acttagggag gctgaggcgg gtggatcacc tgaggtcagg agttcgagac 47220
cagcctggcc aacatggcga aaccccgtct ctactaaaaa tacaaaaatt tatttttgtg 47280
tgtggtggcg tgcgcctata gtcctagcta ctagggaggc tgagacagaa ttgcttgaac 47340
ccaggaggca gaggttgcag tgagctgata ccgcaccact gcactccagc ctgggtgaca 47400
gagcaagact ccgtttcaaa aaaaaaaaga aagaaaaaag aaatatctac tttctagaat 47460
agcccaagta aggtaatttt ttagaaaaat gagaatgtta atgcattttt gttggaaaac 47520
aattagaact ttagagaaaa attaaataga gtttttgtga tctcttaaaa aattagtttg 47580
taaagcattt tctacagttt tgtggtcaag aatgctactg attatattca actgaaaatt 47640
tcttgtccca tttggcctac aatgctttag tttataagtg ggcatgtggc aaatctggaa 47700
agaaatcaaa gtataaggct aaggaagaaa ggtagagaac ggttggtaga aaacaattgt 47760
ctaatgaaaa tgaaaaaggg tgaagaagta gaacatacgt attttaaaaa tattcagagt 47820
atgagacaag gttttgagaa tttaaaagcg attatgtagt tatattaaaa atttagtctc 47880
tttttaagtg tccattgatg aacaaagtgg gaattcctgt tactcatttg caaggcatta 47940
ttgagtgttc agtaacacgt tgcaaggcac ttctgggcaa tcctgaactt ggttctcaaa 48000
ttcttttttt tttttttttt gagacggagt cttgttctgt cccctgggtg gagtgcagtg 48060
gcacgatctc ggctcactgc agcctctgcc tcccaggttc aagcgattct cctgcctcag 48120
cctcctgagt agctgggact acaggcgtgt gccaccacac caagctaatt tttgtatttt 48180
ttgtagagac agggtttcac catgttggcc aggatggtct cgattgtttg acctcgtgat 48240
ccgcccgcct cggcctccca aagtgctgga attacaggca tgagccactg cacccagccg 48300
gttctaaaat tcttttattt atttgtatat gccaaattct gtagtgaaat acgtaattct 48360
gttgtaaatt gtagttcagt acaatttgat tttcactatt caaatctata ccaaaagctg 48420
tttttattgt tgggctgatt cttctacact gttacttgga aataataata taccaggatt 48480
ctttctctta gacttaggag tctttctctt tgcttgcttt ttcagaggct aacagtactg 48540
ggtattcttt aactgtcttg atatgctgat gaaagcacag tgttctgttt ttgaatcttc 48600
tcaaatgtcc ttgtctttga ttcacaactt tttgtcttaa gaggccttca gcatcccata 48660
caaggaaaca agtctttttt tagctgctac ctttggagtt gattttgttt atgtctagga 48720
gcactaaatt atttatactt atactattga aatattcctc tgttataaat tcaaaaattg 48780
actttggaag ataaaatttt agttgaattt aatacatagc actctggaaa gagtattggc 48840
cacaacaaaa aaaaaggttc cctactctat tggataccag gtcatttaac agccatttac 48900
ggtatgcatt gtctttttgt ttttatgatg aattgatatt tcccaaatgt ggaagagtga 48960
atattacttt gagatgtttg tgatagtcca ttccttgctc ctcttcaaaa ttaatgtcat 49020
taaattttta ttactttatt agatcttcat ttctcagata attttagttc attatagaaa 49080
ggcaagaaaa tacagatcag agtgacaact ttgaaaatct cactctactc ataaggggat 49140
gggtgtattt tgctatatat tacaaaatta gttttcttga tgaggacatc cactattgga 49200
gtaatttcag gtatcttatt ttttcttttc tctctctttt tttttttttt tttggagacg 49260
gagtttcgct ctgttgccca ggctggagtg cagtggcctg atctcggctc accgcaacct 49320
ctgcctcctg ggttcaagcg attctcttgc ctcagcctcc cgagtagctg gttactgagg 49380
catgtgccac catgcccggc taatttttgt atttttagta gagacggggt ttcactatgt 49440
tggccaggct ggtcttgaac tcctgacctt gtgatcctcc tgccttggcc tcccagagtg 49500
ctgggattat aggcgtgagc caccacgcct gggcaggtat cttatttcaa aacttacagt 49560
ggtttagtga attatacaat tgcgtccagt gcgtagtatc ctgaaaatag tattaagtca 49620
tgtgtttagg acatcaggtc tcttaagcta agactatcca ggcagaaatt gccctcttct 49680
ataaaagaag aaaagtatta attaggaagt actatcagta tggagaaaac cattttagaa 49740
ttattaattg gcatggtttc cttctttttt tttttatttc gagatggagt ctcactctat 49800
ttcccaggct ggagtgcagt ggtgcgatct cggctcactg caacctctgc ctcctgggtt 49860
taagcgattc tcctgcctca gcctcccgag tagctgggat tataggcaca taccaccatg 49920
ccctgctaat tttttttttt gtttgtattc ttagtacaga ctgggtttca ccatgttggc 49980
caggccgcat ggttttcctt aataacaaaa ttaaggcatt tattactgca tctagatttt 50040
ttttattttt tattagagac ttactcagat tactcccaaa gtaaaggaag gtatggttta 50100
atcaatgctt cttaatgctg ggttcacgtt tagtcacctg gggagttttt aaaaatgttc 50160
tcacttctag ggatcctggt ttaattataa ttagcctggg tgaggctctg gacagtcagg 50220
gtgtgagcta tgggtttcat gtgatgagat cccaggagtg gctctgttct gtggccttga 50280
gaatttgtgc tttctaggcc aggtgcggtg gctcactcct gtaatctcac tttgggagac 50340
caaggtgggc agatcatttg aggtcaggag ttcgagacca gcctggccaa catgttgaaa 50400
ccccgtcttt actaaaaaag taaaaaatta gcgggacgtg atggcacatg tctataatcc 50460
cagctacttg gggagaggct gaggcagaag aatcgcttga acccgggagg cagagattgc 50520
gagatcatgc cactgcactc cagcctgggc aacagaataa aaaaagaatt tgtgctttat 50580
tttcttgcct cacagtcccc tttctgtctc agaattggca actgcctgaa atagtctctg 50640
ctgttatcat ttgatagtac ttttccacat cttgaatgga tagatagagt gttttttata 50700
atagaagtgg atgaatgatt agagtatact aatatgacat tgtattttcc taaaagatat 50760
gaattgattt catttctgag cttttataat tctcttctgt aatagtctgt caaattatta 50820
aggttgataa tattaactaa aatttgagtg catattctat gtgccagact ctgtgctaac 50880
agatttacct acatttgttc acataatcat cacaagttgt ttctgtagta gatacagcta 50940
ttatccacgt catagatgag gaaacaggca tatttaggaa acttgctaaa gtgaggacac 51000
aaatctagct tttctactct aactcatgtt cttaacatta tactgcagtg acataaatta 51060
tgtggtttgg tttgttgttt atctcagttg tcataagtcg aattaatgtt tgtttgtttg 51120
ttttgagaca gagtcttgct ctgtcgccca ggctgggtac agtggcgtga tcttggcgca 51180
ctgcaacctc cacctcctgg gttcaagcag ttatcttgct tcagcctccc taataactgg 51240
gattacaggc acgtaccacc acacccgggt aatttttgta tttttagtag agatggggtt 51300
ttaccatgtt ggccaggctg atttcaagct cctgacctta ggtgatccac ccacctgggc 51360
ctcccaaatt gctgggattg taggcatgaa ccactgtgcc cagccagtaa gttccatggt 51420
tgttaaagga tttctccaca aataaagcta aaagtaaaaa aaaaaaaaaa aaaaaaaaat 51480
tctcaagcaa tataagatgc agactattat gttgttcaag tttttttttt ttttttttaa 51540
tctttggctt tatttttggg gaaacctttt ttttcttttt tgttttcctt gggacggagt 51600
tttgctcttg tcgcccaggc tggagtgcaa tggtgcaatc ttcgctcact gcaacctccg 51660
ccttctgggt tcaagcgatt ctcctatctc agcctcccga gtagctggga ttacaggcat 51720
gtgccaccat gcccggctaa ctttgtattt ttagtagaga ctgggtttct ccacgttggt 51780
caggctggtc ttgaactcct gacctcaggt gatccacctg cctaggcctc ccaaagtgct 51840
gggatcacaa gcgtgagcca ccgcgcccag ccagggaaac ctttattttg aggcggagtc 51900
tcgctctgtc acccaggctg gagtgcagtg gcgtgatctc agctcactgc aacctctgct 51960
tcctaggttc aagcaattct tctgcctaag cctcccgagg agctgggatt ataggcgtct 52020
gccaccatgc ccagctaatt tttatatttt tagtagagac ggggtttcac catattggcc 52080
aggctcttct caaattcctg acctcatgat ccacccacct tggcctccca aagtgctagg 52140
attacaggcg tgagccacca cactcggctg ctggggaaac cttttaacat gagtaaggtc 52200
agtgtgactt ttaagttctt gatgctaaca tcattgattt caataaagtt taaaagttat 52260
attcatgcat atatgcaaat gaataaaagg ctttgaaata gtgacttctt acggtacagt 52320
gaataagttt cctttggtct cttgaatgtt atacatgttc cagtttgatt tactgagaaa 52380
ctgaaagtac ctttacgtca tatgagctgt gagtcacctt ggcacattca taattagaag 52440
agaccatcag attatcattg gaaaatcagt ttgtatttat cctttatttg aattccagtg 52500
cagacagatc tgaggttctc ttcattttgc taaaacttct tagggccttc agtcgctttt 52560
ggctctgtat tcgtgtatct ttggaattgt cctgttatct ctgcttgttt tttacttgat 52620
tttccatcca tttccagtat tcctttctcc tctatttttt tccttcattt tctttctgct 52680
cttcctgttg cgccattatt catgttttcc tctttactcc aactcaacta tggctttact 52740
tctgtttcct tattccattg ttcctcatac tttttcctac tgcttcattt tctttgcagt 52800
attctcagcc tagatgatag gggtcagcaa atctgctcat cagtaaataa attttattgt 52860
agcatagcta tgcccatgcg tttgtgcatt gtctatggct gttttgatgg ctgtagccat 52920
agagttgagt agttgtagct gactgtagga cttgcaaagc cagaaaattt gactgtctct 52980
ttacagaaaa gtttgccagc tcttggccta aatcatattt tccgctgcat ttagggcttt 53040
ttaggactga tcaaaaatac atgctatact ggctttggtg aagtaacaga atgtgctctg 53100
tcctttaaac ttacaactaa ttgcatgctt tgattctaat actgtataat atcctgcgat 53160
tcttattcat gaccattcta attggattta gtctgaagaa ttacttttgc ttaacagatt 53220
ctttgtcaca tttagtgaaa aatcataaaa ggggaaggtt ggttaatgga aaagatctcc 53280
atcaactaac cactaccttc cttatctaca aatttatctt cttcctccgt gccatctttt 53340
tttttttttt tttcagatga tcttgctctg ttgcccaggc tggagtgcag tgatgcaatc 53400
acagctcact gcagcctcga cttcccaggc tcaggtgatc ctctcacctc aacctcctac 53460
ataactggga ctgtatgtgc acatcactat gcctgactaa ttttttatat ttatattttt 53520
tgtagagatg gggtttccct gtattgcaca ggctggtctc aaactgctgg gcctaagagt 53580
cttcccacct tggcctccca aagtcctggg attacatgag tcaccgcacc cggcctcatt 53640
attatttttc ctctggtttt agtagagagg atttttaagc caacttcaat catgcccttg 53700
actctctccc ttctacttac ctccttgttc tctttttctt tttctttttt tttagatgga 53760
gtctcggtct gtcacccagg ctgaagtgca gtggcgtgat ttcagctcac tgcagcctca 53820
gcctcctgag tagctggggc tataggtgcc tgccaccacg cccggctaat ttttgtattt 53880
ttagtagaga tggggtttca ccatgttggc caggctggtc tcgaactcct gacctcaagt 53940
gatcacctgc ctcagcctcc caaagtgctg ggattacagg cgtgagccac cacgcctggc 54000
catctttttt tttctccttg ctcttttata ccacttctct gtttctgggc tcttcaacat 54060
ctgcctttct agttaatctt tccctttagc atgaaaacct attcacttcc tgctcatcct 54120
aaaaaggatt cttttttgtt ttgttttgtt tttgtttttg agacagagtc tcgctcttgc 54180
ccaggctgga gtgcagtggc actatcttgg ctcactgcaa gctccgcctc ccgggttcac 54240
gccattctcc tgcctcagcc tcccgagtag ctgggactac aggcacctgc caccacgccc 54300
agctaaattt ttgtattttt agtagagatg gggtttcacc gtgttagcta ggatggtctc 54360
gatctcctga ccttgtgatc catctgcctc ggcctcccaa agtgctggga ttacaggcat 54420
gagccaccgc actgggccca aaaggattct ttttaatcct gaattcttct agccattatc 54480
ctgcctaagg ctacgattaa cctctaactg ccaggtcctt tggaatcttt ttctgtcttt 54540
attgctgcac ttgaatgttg gtttcaccct ccttcagaat ttcctcttct gtatttttta 54600
tgtttattga tcattccttc cctgcctcat tcctgggctt cttttccttc acacacccct 54660
tagatgtgtg tccccagtgt ttgtttcttt gcctgctgct cttgccacat gacacacact 54720
gccagctacc acacacaagt tccctcctat catgtgtgta tcattgccct tataccatgt 54780
tgtattaaaa ttatatgctt gtctcccctg ttacagtttg agctctttgt gctccaagta 54840
aagacagtga tactgtcttt attatttatt ctcatggtct agtatagtgc tttggcacat 54900
agtacaggct caatataaat gtgtttgaat aaatgaaatt cagtgcctta atacactttt 54960
gtagaagcat tattttatgg aaagaatgaa aaagctgtaa gtggtcttac atatatagtc 55020
atccagcaga tacttagaga gctctgggat gtgttccttg ctgtgcttgt tgctatggac 55080
agtacggaga aatacaagaa tctattttgg gtcccttttg agaacctagt gaaactgtgt 55140
acctagtgaa actgtatacc ctcaccctag aaaaatttac acacatgtag attttacatg 55200
taattctttt aaaaattaat tttttttctt ttttttaaag aaacagggtc atgctctgtc 55260
actcaggctg gaatgcagtg gtgtgatcat ggcttactgt agcctcgacc tcctggctca 55320
agcgactctc ccacctcagc ctcccaagta gctggggcta caggtgcacg ccgctatgcc 55380
cggctaattt ttaaaaatat tttatagaca ctggttctca ctatgtttcc caggctggcc 55440
tttacctcct gggttcaagc aatcctctac cttggccttc aaaagtgatg ggattatagg 55500
tgcaagccac tgtgcccacg ctaatgtaat ttcatggtgt tcacagtttc ttcagggagt 55560
tcatatacgc catgtactct attctaagca tttttagagt tagagatagc aaagcacgtg 55620
aataaattca agaaaaatgg aatgttgtac tgcatgacat tgaatatcaa atggagtcag 55680
cgatgcaaat aattgtctag attttacaaa aaaaattagc ctggtgtgct ggtgtgcgcc 55740
tctaatccca gctactcggg aggctgagac aggagaatca tttgaaccca gaaggtggag 55800
gttgcaatga gctgagatcg taccactgca ctccagcctg agtgacagag cgagactcca 55860
tctcaaaaat aaaaaataaa agaattgtgt agattttagt agttggaaga agttggagtg 55920
ttaatgtgta attagagaac agtgagaaat aaaattctac agattgtttt attctggtgt 55980
gctgttgtgt tctcatatgg ttgtcttttt ggtcttgata gtgtatcagt aacagagtac 56040
gagtaacaaa cagggatctc ttctgaacgg cgtgacatta gaaaagctgt ttacggcctc 56100
aactttgctg tggtttatta agacacagat atgtgttcat tctggggcca agcagtaact 56160
ggagagtggc acttattgag gccagtatgg aggcagtaca gagattattg agattaaaag 56220
aaagaaacag gtggaacgga tctatgtaat ggaaagctaa acagaatagt tcgtggtaca 56280
cagtagaaaa gcattacatg tttattaaga tatggtcatc ttccatttat taaagttaca 56340
tgttttataa tttttagagt atatagaaat tctctaccct atcatgtttg ccaaagtcag 56400
aacaataact tcatttatta aatataaaaa aaataaaaac ctctagcata aaatagaatt 56460
ttatttggac aaacgataaa aaaatactgt gtggtactag taagagtaag gttgattcaa 56520
gatacatggg agcagaatcc aaagtgtaga aataggccag gtgcagtggc tcatgcctgt 56580
aatttcaaca cttttggagg ctgaggcggg aggatgagtt caggagttca agactcgcct 56640
tggcaacttg gcaaaacccc atctctacaa aaagtacaaa aattagccgg gtgtggtggt 56700
gtactcctgt aaacccagct acttggtggg ctgaggtgag aggttcactt gcagccagta 56760
agtcaaggct gcagtgagct gtggttatgc cacggcactc cagctgggtg acaagcaaga 56820
ccttgtctca aaaacaaacc agccaggcgt ggcggatcac ctgaggtaag gagttggaga 56880
ccagcctggc cgacatggct ctactaaaaa tacaaaaatt agctgggcga ggtgacgggc 56940
acctgtaatc ccagctactt gggaggctga ggcaggagaa tcgcttgaat ccaggagacg 57000
gagtttgcaa tgagccgaga tggtggtgct gcactccagc ctgggtgaca gagccagact 57060
ctgtctcaaa aacaaaaata agcataggac atggggataa attgaagatt tatgaagaca 57120
cagctgaagg agacataaaa gtagatttgg ctaaatggaa acatgccata ctttgaatgg 57180
aattatttaa tactacaacg ttgtcaattt tcctcaaata aatctctaaa gataatatat 57240
tcagttttgg ccgggcacgt tggctcacgc ctgtaatccc agcactttgg aaggctgagg 57300
tgggccgatc acttgaggac gggagtttga gaccagcctg gccaacatgg tgaaaccctg 57360
tctctactaa aaatacaaaa atcatctgga catggtggca ggtaccagct acttgggaag 57420
ctgaggcagg agaattactc gaaccccgta ggtggaggtt gcagtgagct gagattgcac 57480
tccagccggg tgactccatc tcaaaaaaaa aaaaattttt ataatatata tatatatatc 57540
cgtttttgta gaaattgaca aaatgattct aaagcttatt agattatgtg tattaacaga 57600
agaactttgg aaattttttt ccacaagagt cataaaggag gacttgccct acaaaatatg 57660
tcagaattaa aacataactt gtcagctggg tgcggtggct cacgcctata attccagcac 57720
tttgggaggc tgaggcaggc agatcatgac cagcctgacc aacatggaga aaccccgtct 57780
ctactaaaaa tacaaaatta gccggtcatg gtggcgcata cctgtagtcc cagctactcg 57840
ggaggctgag gcaggagaat cgcttgaact cgggaggtgg aggttgcagt gagccgagat 57900
cgcgccattg cactccagcc tgggcaacaa gagtaaaact ctgtttcaaa aaaaaaaaaa 57960
aaaaaaaaag aattataact gtcacagtgg ctacgtatgg agcatccaaa actgaattta 58020
tgtgggtatt ttattaatat gcaatatagc actttaattc tggaggaaag gtggattatt 58080
cagtaaatga ttctgggaca ttggggacaa attagatacc tacttcacac tgataaataa 58140
aaccaaatag attaatgaga aaactgtgat taaacaaaac aacacccaga ctacactgga 58200
gcaaatctgt gaatttgttt aattttgagt ggagaaggac tttataagca tgactaccag 58260
agcaaaaaaa tcatgaagta aaagatcgat acctttgatt ataaagagat taaagattta 58320
ggccgggtgt ggtgctcacg cttgtaatcc cagcactttg ggaggccaaa gcgggtggat 58380
cacttgaggt caggagtttg agaccaacct ggtcaacctg gtgaaacccc atctctacta 58440
aaaatacaaa aaaattagtc aggcatggta gcacatgcct gtaatcccag ctactcagga 58500
ggctaaggca ggagaattgc ttgaatttgg gaagtggagg ttgcagtgag ccgagattgt 58560
gccacatcac tccagcttgg gcgacagagt gactccatct caaaaaaaaa aaaaaaaaag 58620
acttagacgt gtccaaaagt accatacatt taaaaagaca tgccacaaac tgggaaaagt 58680
agaaaaatag ttttaaaaat gaccagtgaa tgtatgaaaa ggtggccctc ctcacttgta 58740
atgatttaag aaatgcagtt tatttttatt ttattgtatt tttaaagaaa ttcagtttta 58800
aagcagtgga atatgattgt ctatcagctt gcgctgaatg gtaaatgtga gaaagattac 58860
tactacttag tggtactgag ggagttgcaa aacacttaac actgctagtg ggatggttta 58920
agtaaaacaa gtagcattct taaactctct attaggtaaa gaataggtaa gtaatgcata 58980
tgtttccagg acattttcag taagactgtt tactgatagg gttgtgtaat gctaatatac 59040
ttactatcta gttttagtat tatttttttc tcttgtcttg gatggtttca atggagtctt 59100
atgcatgcag atatattaaa actagtaata aagcaagaga aggaatgtgg ataaattatc 59160
tctaatttct attttgttct atttctattt catactcctg ggaaagaata ttaagtgggc 59220
atgtgtactt gaacagttgt tctgtttttt attagaaaag aatccgaatc tataaaatgt 59280
tttacatatt tgccagggaa acagaaaaga tatttgtaca gctgtaagaa ttggaattaa 59340
tttcatttta ctgacttttc cttaacctaa ttctgaacac ttttgccata ggtttgagaa 59400
taagttgtta taaaatgact actattcttc actaatagta ttggcatttc aattcctaaa 59460
ttctgttttt tgattcttga acatttctga atttactttt tttgtcttag ttcttctaca 59520
gaatcatttt cttctttttt ctttttttat ttttattttt tatttttgag acagagtctt 59580
gctctgttgc ccaggctgga gtgcagtagc gcgatctcgg ctcactgcaa gctccgcctc 59640
ccgggttcat gccattttct cctgcctcag cctcccgggt agctgggact agaggtaccc 59700
gccacagcgc ccggctaatt ttttgtattt ttagtagaga cggggtttca ccgtgttagc 59760
caaggtggtc tcaatctcct gacctcgtga tccatccgcc tcggcctccc aaagtgctgg 59820
gattacaggc atgagccatc gcacccggcc ttcttttttt ctttctcttt aacttctgag 59880
ctgaaaatag taccttttat aaagaagtgc tcaaacgatg attggactga tttctcctta 59940
tttctctctt tctctctgtc tctttcactc tctttttaga atttttcttt tttaagtaga 60000
gacgaggtcc cactatgttg cccaggctgt cttgaactcc tgagcccaag caatcctctt 60060
tgcctcagcc tcccaaagtg ctcggattac aggcttaagc tatcacacca ggcctaggct 60120
aatttcatat tttgagatgg cacaaatttc tttcaggtag ctagcttttc ctcctcctcc 60180
ccacttaaaa tagatcctga tccagaagcc taatggagaa aatgaaaaca gaatgttcac 60240
ccataaacag tatctttgta ttggaatctt ttctaaaact tcttttgatc tttttaggag 60300
atagtgtggg aatcagcaat ctagtattac gtacgtggaa tctgtcacct tgttttttta 60360
aatacagcaa acctcatgaa gtgaatttcc atattttttc ttgttcttgt tagttttgca 60420
ccactcaggc tttgctgtag aatttgatgt atatttgatt ctgtagagca tgggctattg 60480
atcttcactc agctttcaga ggaatctgat tagtaagttt gagtttttta ttatttttta 60540
gttgattttg aagtaaaata cagcaccatt ttaactgata ccatttctaa acaattttca 60600
gttcaaattt taagttagct aatttagagc ttaagaaaat tgctttaaaa acataaaatt 60660
actggctggg tacagtggct cattcctgta atctcagcac tttgggaggc caaggcagat 60720
gaattgcttg agcccagtag ttcaagacca gcctgggcaa tatggtggaa ccccgtttct 60780
acaaaaaaaa tacaaaaagt agccagacac ggtggtatgt acctgtagtc ccagctattc 60840
gggtggcaga ggtgagagga tcatctgagc gcagggagat tgaggctgca gtgagccaag 60900
tgagaccctg gtttcaaaaa aaaaaaggtt actaattgca gtgcctttta tcttatttaa 60960
tgggcttagt caaactaaga tgatgtattt tatcttataa atgttttccc ttgaatttta 61020
actgaagaat ccaatttgta cctctcacaa acagaatgta ttagtaagga aaataaatac 61080
tgctttttat tacttaaata ggatatattt ttctcttagg gatttttttt ctattttatc 61140
tcactttatc gtagtgctag aaaatttaat cattcatttg agatagggag aaaattaggt 61200
tttttttttt cttctatttt gagacagggt ctcattttgt tgtccaggct ggagtgcagt 61260
ggcgccatcg tagctcacca taacctcaaa ctcatgggtt caggtgattc accttagcct 61320
cctgattaag ctgggactgc agatgtgtat caccactcct ggctaatttt tgttgttatt 61380
ttttgtttga tgaggtctca ttatgttgcc caggctggtc tcaaactctg ggcctcaaat 61440
gatcctcctg ccccagcctc ccaaagtgct gggattacag gcatgaacct ctgctcccag 61500
cccatttttt aaaatatatt cacagcattg tgcaaccatc actacaatca atttacattt 61560
tcatcaccct gaaaagaaac tctgaacccc ttagcagttc ctctctgttt gtttcaattt 61620
tccccagctc caggcaacta ttgatttatt gtcttcatag gtttgcccat tctggacatt 61680
gcgtattaat ggaatcatat aatatatagc cttttttttt cttttttttt tttgaaacag 61740
agtctcactg tgtcgcccag gctggagcgc agtggcatga ttgcagctca ctgcatcctc 61800
tgcctcccag gttgaagcga ttctcctgcc tcagcctctt gagtagctgg gactataggc 61860
gcctgccacc acacctacta attttatatt tttagtaaag acggggttgc accatgttgg 61920
ccaggctggt ctcgaattcc tgacctcaag tgatctgccc acctcggact cccaaagtgc 61980
tgggattgca gccatgagcc accgcatctg gccatatata ttatgatagg cttgtttcac 62040
ttagtatgtt tcttccatgc tgtagcatgt attagtactt ctttcttttt catggccaaa 62100
tattccatta tacagttaca caggtacact acattttgtt tattcatcag ttggtggaca 62160
ttttcattgt ttccaccttt tgatttatac ataatcctgc tgcgaacagt gacttttaaa 62220
gtttttgtgt gggccgggtg tggtggctca tgcctctgta atcccagcac tttgggaggc 62280
tggggctggc agatcatttg aggccgggag ttcgagacca gcctgcccaa catggtgaaa 62340
ccctgtctct actaaaaata caaaaatgag ctgggtgtgg tggcgtgcac ctgtaatctc 62400
agctactagg gaggctgagg cagagaatca cttgaagctg ggaagccgag gctacagtga 62460
gccgagatca cgccactgca ctccagcctg ggtgacagag tgaaacttca tctcaaaaaa 62520
aaaaaaaaaa aaaaaaaact gcgtgtggac ataggttttc aattctcatg ggggtgtgtg 62580
tgtatgcata ctcatacata catacacata cctgcaagat aattgctggc tcgtatgcta 62640
aatctatgtt gaacctttta cataactgtt gggctgtttt gttttctttt tattattttt 62700
tgaaaataga gttggggtct cactgttgca caggctgatt tcctgggcat agtggctgta 62760
tcattttaca atcctacata gctgtttcca acgtagctgt atcattttac aatcctacta 62820
gcagtgtctg aggtttctta tgtttttcac atcctcacca gcatttgtta ttgtctgtct 62880
ctttgattat acccatccta gtgggagagt aagaagtagt atctcactgt agattttttt 62940
tttctgttta caactttact ttaaaaatta tatatgcaca catggtaaaa agttcaaaac 63000
gtgtgtacca aaagatttaa cagtgaaaat agaaaataag tgtggtcctt gttttcttcc 63060
accaaggcaa atattgttat aatctcctaa acaacttgtc ttccagattt ctcattttca 63120
gtcaatcttg ggcattgaca taaagaaatt cttagacatt gcttttatta gatcatctca 63180
tcccttgctc aaaatcttca gtggccactg ttgtttacag aataaagttg ggatgctata 63240
cagggccctt cccagtggaa cttctctttt tcaaccttat ctctcattat ttcccaatgt 63300
tttttttttt ttttttgaga cggagtctcg ctctgtcgcc caggctggag tgcagtggcg 63360
ggatctcggc tcactgcaag ctccgcctcc tgggttcacg ccattctcct gcctcagcct 63420
cccaagtagc tgggactaca ggcgcccgcc actacgcccg gctaattttt tgtattttta 63480
gtagagacgg ggtttcaccg ttttagccgg gatggtctcg atctcctgac ctcgtgatcc 63540
gcccacctcg gcctcccaaa gtgctgggat tacaggcgtg agccaccgcg cccggcctat 63600
ttcccaatgt taatctactt attgacctac taagctggca tgttctgtgt gttagacatc 63660
accaactttg tgccttcttt ttttgtttgt ttttgagttg gagtctcact ctgttgccca 63720
ggttggagtg cagtggcgcg atcttggctc accacaacct ctgcctcccg ggttccagtg 63780
attctcctgc ctgagcctcc cgagaagctg agacgacagg cgcgcgccac catgccctgc 63840
taacttttgt atttttagta gagatgggtt tcactgtgtt tcccaggctg gtctcgaact 63900
cctgaccttg tgatccacct gccttgggct cccaaattgc tgggattaca ggcgtgagcc 63960
accgcggccc cctgtgcctt cttcttttac tcctggattt aatcccaacg tgaagaatct 64020
accttactaa ctagagtttt agatactttt tcaaaaccaa gcccacatct gtccttttta 64080
gagtcttctc tgaccttccc tgctcattgt ggtttgtttt tattgcctgt aacaatggct 64140
gttaaacttt acattttaaa ttaatttatg tttgtatgta tttatttgtt gagaaagggt 64200
ctctctctgt cacccctact agaatgcagt ggcgccatca tggcttactg cttcctgggc 64260
tcaagctgtt ctcccatttc agcctcccca tgcaccaccc tacctggcta atttttttgt 64320
ttgttttttt tagtttagtt tttgtagaga cagatgtctc actgtgttgc acaggctgat 64380
cttgaactcc tgggctcact tgatcctccc atctcagcct ccccaagtgc tgggattaca 64440
ggtgtgagtc accatgccca gactttaaca ttttcttttt agtatagaat aggtcagttt 64500
ttttccctct gatgagatcc catgctgact cttagttaaa acaaggcttt ggttggaaga 64560
agagctagtg atgtcctagc tccctactta ctccactttc ccttgccttc tggggtgtcc 64620
tgaagacatc atagggtgtc atgaagtaca gttggagaac cagtggtctc catcatgtac 64680
caaacactca tcttcacgaa gcagtatgta gtgtcttttt taccggtata ttttctctct 64740
cccaatgcat taaacttttc tggagttcag aaaacaaatt tatagaatta aggaaatgcg 64800
tcccccccaa ccatggtgtc tagtatatat acagtgactt acagataaca ggtgttcaac 64860
atatatatat tcctttgatt gatttttgaa aagtttacat gtatatattt tttatatacg 64920
gggtctcact ctatcactga ggttggagtg tggtgatgca gatcttggct caccgcaacc 64980
tcctcctccc aggctcaagt gattctccca cctcagcctc ccgagtacct gggaccacag 65040
gtgcgcatca ccatgcctgg ctaatttttt atatttttgg tagagacagg attttgccgt 65100
gttgcccagg ttggtttcga actcctgagc tcaggcagtc cacctgcctt ggcttcccaa 65160
gtgtgagcca ccactgaaat acttatattt ttaaacttaa tttatttata tttattatat 65220
ttttatgttt ttatatttta aaaaatattt ttatactcac tagacccaat tttatactcc 65280
taaaccaggg aataactgtt tttttttctc ttacataggc atgataccat agacaatgat 65340
taaaattgta attaccattc atttcttagt tttgtggctg ggacactgat gtcttcaaat 65400
gttagtttgc aaatacagtc agccctctct atccatgggt tacacagctg tgaattcaac 65460
caaccatgga tccaaaatat atgggaaata cgctggggct gtgggtcaca cctgtaattc 65520
cagcacttag ggaggctgag gcagatggat cacctgaggt caggagttca agaccagcct 65580
ggccaacatg gcaaaaccct agctctacta taagtacaaa aaattagctg gccatggtag 65640
tgcacatgtg taatcccagc tactcgagag gttgagacaa gcaatttgct tgaacctgag 65700
aagtagaggt ttccatgagc tgagattgtg tcactgcact ccagcctgcg caacagagtg 65760
tgagaagaaa agaaaaaaaa ctgtctgaaa agaaaaaaaa aaattatatg ggaaatcaaa 65820
agcatctata ctgaacatgt acagactttt tttcttgtca ttattcctta agcagtacca 65880
caactatttc cgtagcattt actttgtatt aggtattata ggtaacctag aggtttaaag 65940
tatgcgagag tatgcaaata ctacaccact ttgtatcagg gacttaagca tccctggatt 66000
ttggtatccc tagggggtat tagaaccaat cccccataga tgctgaagga caactgtagt 66060
gtgtgttgga ataatttatt ttcaaatgga tcatttggag aacactattc tttaggaaac 66120
atagcctcct aagttctgtt ccatacatcc ctttcacctc cacggcgttg tagcatcctg 66180
ctttcatgac tgtgtcatca ctcggaagga actgcttctc ttccagaatg cttttcaaga 66240
tctactctga ccacagctat aaactttaca cttctattct cttcttgccc ctcacagtgt 66300
tctctgttcc tctaagatct taaactctgt ctactcctaa tccagcctgc tgggtgtggc 66360
tggagaaagt cccactgggg ggctgattag ttaggaatgt agggtttcca gctcttgctg 66420
gagcctcaga agagttcagc agactttttt tttttttttt ttccttaaac ctatttctgc 66480
agccttgatg accactcctt ccagtccctc acctatttgc tttattcatg gcagaggctc 66540
tttcttcctg cttgtcagta caaagaggca ggattcttca cctggatctg tggattctca 66600
aagaatttgt ggagagaatt cagggcattg atgaccttgg atgaagagaa atttacatct 66660
ttatttacac taaccttcaa gtgaaattta gcattttttg ccatttaaaa atatgggcaa 66720
caaacaacta gtagtattag cagtatttat gacttaagca cctatagaac tcagttaatt 66780
tcatatcgct tgatgttatg ggtatctcaa attattattt tatgtatata tatttttgag 66840
atggagtctc gctctgtctc ccaggctgag tgcagtggtg cagtctcagc ccattgcaac 66900
ctctgcctcc tgggttcaaa cgattctcct gcctcagcct cctgagtagc tgggattaca 66960
ggcgcacacc accacgccta gctaatgttt gtattttcag tagagaaggg gtttcaccat 67020
attggccagg ctggtcacca actcctgacc tcaagtgatc cgcctgcctt ggcttccaaa 67080
gtgctgggat tacaggtgtg agccaccgca cccggcctca aattattttt agaaacagaa 67140
tcttgatatg gtatccgctc tggccttgaa cttgtgggct caggcagtcc tcccacctca 67200
gcctcctgag tagctgggat tataggcatg tgccactgca ccaggcttca aattattatg 67260
tatgttcatc acctctttaa atttataata gttattaaac ctgttactgg atcttaatat 67320
ttaatgcttt aattaagaac atgtatgtta ctatgccaac agattttttt agtttttgat 67380
aactgcattt cattgttact tgttctcatt tgatttcctg tgtattttac gaatttaagt 67440
acattctgaa tacggtttca taggcttccc taaaatattg aaggggccca tggattaaga 67500
aaaaggctaa gaatccctaa tctagaggct ccccacagtc ctcttttgtc atcatacccc 67560
taccccattc tagcctgagg agcgtggctc cacctgtgcc cttggttttg ttgttccagt 67620
ccatacatcc tgcaccctta actgtgtttc ttatccccaa cttgtttctt tgtgttattc 67680
ttcagtatta tagtctttaa tataatctgt ataatacatg gtgtagtagt atatgctcgt 67740
agtatacaat tcagttagaa cagatgagta ttcaatgaaa agataatctc ctctctaacc 67800
cccagtccca cttccctggg gaagcctgtg ttcttgtgta caattcagaa aatgtttata 67860
cacatatttt ttatttattt attttttgag acggagtctc gctctcgcca ggttggagtg 67920
cagtggcgca atcttggctc actacaacct ccgcctccct agtagttcaa gcaattcaag 67980
gttcaagcaa ttcgcctgcc tcagcctccc gagtagctgg gactataggc gtgtaccacc 68040
acgcctacct aatttttgta tttttagtag agacagggtt tcaccatgtt ggccaggatg 68100
gtctcgatct cttgacctca tgatccaccc gcctcagcct cccaaagtgc tgggattaca 68160
gatgtgagcc actgtgccca gcctgttgat ttaattttaa acagagtttc gctcttgtta 68220
cccaggctgg agtgcaatgg tgcgatctcg gctcaccgca gcctctgcct cccaggttca 68280
agtgattctc ctgcttcagc ctcccgagca gctgggatta caggcatgca ccaccatgca 68340
cagctatatt tagtagagat gggggtttct ccatgttggt caggctggtc tcgaactccg 68400
gacctcaggt gatccgcccg cctcggcctc ccaaagtgat gggattacag gcgtcagcca 68460
ctgcaccccg cctatacaca tttttttgtt ttttgttttt ttgagatgga gtctcgctct 68520
gttgtccagg ctggagtgca gtggcgcgat ctctgctcac tgcaagctct gcctccctgg 68580
ttcacaccat tctcctgcct cagcctcccg agtagctggg attacaggcg ccggccacta 68640
cgcccatcta actttttgta tttttagtag agatggggtt tcaccgtgtt aaccaggatg 68700
gtcttgatct cctgacctcg tgatctgcct gactgggcct cccaaaatgc tgagattaca 68760
ggcgtgagcc accgctccca gctatacacg tatttttaat gccactccag tctatgttgg 68820
aaccatttta cttccccttt cttattttct tcttgtgttc ttgaaggcct agatcagctg 68880
ttgctgatag gctgtcactg tcactttaga aagcccagag ccttttgttc cttagaactt 68940
tgtttttaat tgtattgtag cactcattgt attcgattct aaaagatttg cttcatttct 69000
gtaactagtc tcttacaccc aggagctcct agttcctaca ggaaatgctg ggaattgtat 69060
cagtcaaatg tgaatcccca cctcgtccag acttatgagt gcattgtagg tactcagtaa 69120
gtgctaaaaa tgactaaata gtcccactga taccaatcta tatactgata ctttatatag 69180
tatatagatt ggtccacata taacgatgac acataatgag aaactgtctt aaaaagttgt 69240
tgaaagtgcc gcaggaatag gaattgatca aaacaatatg attttttagg tttatatgga 69300
actttgatgt ttgagaaaag gctgatttag ttgagaagaa atggttagct gaggattttg 69360
atgacttctc tggaagcaca tttgagggtt tgtgatgtta aatctgatgt taatgattat 69420
ttcatccagt tttatgtcat tttatagttt ttatacattt aagtatattt atttctaatg 69480
tttaacacta ccattttagt tatttgacca ttattctggc cctttaaaaa atgctcagac 69540
aagtttgaat gatttttcag aggcattatt ggctcagagg taaaagagga aagattgaga 69600
agctgaatat gtactctgtt tcctgggtat ggggctgggg atacccagaa gaggttcaca 69660
cgttggtcga gacatttctt tatgaccacc agcaggtggc atcaccggcc caaaatgact 69720
aagtttctgc ccagaatcag aagagaaggt gttgagagcc cactgctgtg ggggtagcat 69780
ggaggtggga tacaggggct ggaggtgata caattttgtt tcttcctcca acatcgcctg 69840
ctagtctaga ggcttttata aattgaaaaa ctaattcttt atcatctcat ctgatggttt 69900
ttatgttttt ccttttttct ctctatacct gtagttcctt cagaaacagg taacactttt 69960
ctaatagtca cgttgtattc ttgcatcttg ttgttacaat gcttttgttt ctcaccatag 70020
gggatgatgg aaaattaata ttctttgact tatggcattg gtaaaatctg catgcaaatt 70080
cccacagttg cctgtagatt agagccagtt gtttttttct caactttgca ggaatcctgg 70140
ttacaacatt gtactattta ctaccaacag tgtttttttt ttttaaaatc cagacttgct 70200
gggcatagtg gctcatgcct gtaatctcag cgacttggga ggctgaggtg ggaggattgc 70260
ttgagcccag ggctgcagtg attgcggcac tacactccag catgagtgac aaagacccca 70320
tctctgaaaa aacaaaaaca aaaacaaatt ttttttaaag aaacagaaac aaaaatccaa 70380
acttgtaacc actgtaaaac aaatcagaat ttacgatagt ggatattatt aatagtgcag 70440
aatggatacc cagatcttgc ttcctttcta gctaatgatg caatgttggc ctgaaatgca 70500
ttacttatag ccagggattt tctcagcatc ctgatgatat agcctcattt cgtgctaact 70560
ctccacttct gcacatcttc ccctaagtcc tttactcatc tttagaaaga gctacttttg 70620
gtgaaatttt aaaaccaagg aatatcattc tttatagaat cacacttctg tgttttcccc 70680
ttccccattt ctgtctcgaa agcgacagac tgctacataa cctgtgaata ctttttttta 70740
aaaaaagttt ggtattgtaa acagaagatt taagattaaa atgtagcatt gagaaaaata 70800
gatttattaa taatgccctc ttaacacaac ctaaattctg gtcagtggaa taaagcctgg 70860
gtcctaaagt tttagacgct tgcttgcttt tccacactgg ctcttacttg gggatccttt 70920
tagaaatttg tttagaataa tactgtaaaa acatatttaa gctactttgt gtgtacattt 70980
gggatctttt ggtttgaaga cggcttgact caagactttc taaatatttt cacacacaca 71040
cacataccct gtagtgagaa aaaaatccgt ttatatggtt ctataaaaat ctctagctgc 71100
ttcgagcttt aatttcttga atcaaaagag tattgttttt aatactgagc ttctatctaa 71160
ataaatgctt tatttactta aatgtgtgct tttcaaaaac tagtatgatt aagacattaa 71220
caggatctta gacgtaaagg aacagtcctg ttgcttcttc cagaagataa tatgactcgt 71280
ttggaatttt cctatagtgt agttttttgt ctagtgttgt gagaattaaa gggatttcag 71340
gatcttaagg taggttatta tttgatgttt tcttggaaca ttttacattc ttgaaaatac 71400
acatggctaa attaattttt gccagcaatc cacataactt taagataatg tagagaagaa 71460
cgtgattcag gttagtatca aataaggtca gatttctagt gccatcagta gctttcagca 71520
aagatgaggt gttggtaaga tagcattagt ctcttagaat ctcttagaga gattttccaa 71580
aattcagcca tttctagtga atgctccatt ccacccccag ctgagtcctg ctgctctggg 71640
gaactccctc agcacactct tggctcttag aattgctagc aatgggagta gtgctgctgg 71700
tggagctggc agctaagccc agaggtggat taatgctttt attccctgat gtacaggtac 71760
acacactcat acctacccac acctagtttg ggataagaag aggttagaat tagctaggct 71820
tgaagttcca tgcttaaatt tgctggctca gatttcttat tttggcatca ctttgcccat 71880
tagggagaca atgacagtta tagaagcatt gccaaataaa aaatccatct ggaataacct 71940
cttttgtagg agtattgtgt gtttagttgt tgattcgtcc cttcctcctc ttagtggcaa 72000
cttacagtac tgggaaggaa cagtggctgg gagcttatat tcctcagcag agccagatca 72060
gcagaagtat tactccttag ttcgtagtag gtggtaccct atgggtccag tcatttaaat 72120
gcaagcctgt atctacagag cgtttcctag tgccatcatt gcccagtggg cctttattta 72180
gctgagtcta actcccaact agagaaaatt tcctgtgcca gacagcagta tggtcagcta 72240
acatgtggat gctacatttg ctttcataag tcagtactct tcaataacat tagtagaaga 72300
gaagaggaca caaagtgaga gtgtgttaat aggaagtcca ggtatgcctg ctacctgaac 72360
tttctgagac aggtaatact gtagggcctg aactttgtag cagagtggtt atatatgaag 72420
aagtgggttc tgggaggggt taaaccactt agaatggctt catttactaa tggcaagagt 72480
ttgctgggat attgaccact gtacatagac atgaatatgg aaagttaaaa acaaaatcca 72540
catatatttg gctgcaagta ctccgaaggt atatctaatt agtgcatcca ttaaacaaaa 72600
gagatatttt aggccgggca tggttgctca cacctgtaat cccagcactt tgggaggcca 72660
aggtgggtgg atcacctgag gtcaggagtt cgagaccagc ctggccaaca tggtgaaacc 72720
ctgtctctgc taaaaataca aacattagct gggcgtgttg gtgggcgcct gtaatcttag 72780
ctacttggga ggctgaggca ggagattccc ttgaacctgg aaggtggatg ttgcagggag 72840
ccgagatggt gtcactgcac tccggtctgg gtgaaagagc aagctccatc tcaaaaaaga 72900
aaaaaaaaaa aagagatatt tttgatggat tgatagaaat tttctttttc tttttttttt 72960
tgagacaggg tctcactctg tcgccaggct ggagcacagt ggcgtgatct ccattcattg 73020
caacctccac ctcccgggtt caaacgattc tccttcctca gcctcccgag tagctgggac 73080
tacaggcatg tgccaccatg cccaactaat ttttgtattt ttagtagaga gagggtttca 73140
ccatgttggc caggatggtc tcgatctctt aacctcatga tccacctgcc tgggcctccc 73200
aaagtgctgg tattacaggc atgagccacc acatctggcc agaaattttc ttggtcactt 73260
ctgagacatg cagagtaatt acctgtaata taatttaatg aattatgtca atatattaaa 73320
atatgcttca tgtgggctgg gcatggtggc tcatgcctgt aatcccagca ctttgggagg 73380
ccaaggtggg ggtatcacta ggtcaggaga tcaagaccag cctggctaac acggtgaaac 73440
cccgtctact aaaaatacaa aaaattatcc gggcgtggtg gtacacacct gtagtcccag 73500
ctactcggga gactgaggca ggagaatcgc ttgaacccgg gaggcagagg ttgcagtgag 73560
ccgagatcac gccactgcat tccagcctgg gcaacagaac gagactctat ctcaaaaaaa 73620
aaaaaaaaat gcttcgtgtg gcttaaaatt atatgaaaag aaaatacctt tactgatagt 73680
catctgtgat tccatttgct aaattaaacg tgaaagcata cttttactga atactatata 73740
ttccgtatca gtttagatag cagtttatct tcacatacat aagttttaag tttaccttta 73800
ttatagtgca ttggtctttt gttttcatca acctaaatta tgttcaataa atgtttctgt 73860
tagattttaa gttaaacaat tatgtgaaat tcatttttcg taattgtttt ttaacatatg 73920
tctttgttgg taattcacgt gtgtgagtgt aactgattgc cagattatat aaactttcaa 73980
ccaaaaccat tctttgcaga tgcttttact gactctgcta tcagtgctaa agtgaatggc 74040
gaacacaaag agaaggacct ggagccctgg gatgcaggtg aactcacagc caatgaggaa 74100
cttgaggctt tggaaaatga cgtagtaagt aacatctttg taattattgc tagactctgg 74160
tcagtatgac atcctgtcac ttggttgtaa tttaaatgtg cttttgttgt tgttgttatt 74220
gtagtgagtg tatttagagc agcaggtttg ttgtataact agagactttc tcccaagcaa 74280
tatataaaga aaaatgtttg tcattttact tgtaggggtt aagcaggagt actgtctgtt 74340
cttgtggatg ctcatgaatt acttctttgt gattaaaata aataataaga agtagcttaa 74400
attaaaatta gaaaccatgg gaaatgccgg tgtgttttgc tttaacaccc agccaaataa 74460
ggtagcctaa ggaaagtggt gtcttaattg ttgacttcac ctagagaaga ggttgaagta 74520
ggacatttta agcctcttgt ctgaagaaaa ggttgtcatt aagataaata attaggttac 74580
attggaatta aagcattaca taaatttctt ggtcttaaat ttggattatt ctccacaaaa 74640
ttcttttatt tctaaaacgc ctcttgtcac atactagttt tgtttctctc tttaatgcat 74700
tatctgtact tgaagtgctt agctgggtat gctggcacat gcctgcagtc ccagctactt 74760
gggaggctga agcaggagga tcacttgagc ccaggagttg gagtccagcc tgaatgacat 74820
aaggagaccc cttctctaag aaataaaaat aaaaacaaat acttaataaa gactctgtct 74880
ttaggataga gagcatagag atataaagca aagtgtcttg ccaaaaatga gtgttatggt 74940
accaatattt gagtagaatg aagaatcttc cattgagtag aaagagaatt tgtaacatat 75000
ctgtgtttga tgtttaaggc ataacagctt aataatgaca ctcttcctca gacaggaagc 75060
ctgaaatgtc ctactttgac ctaaagtcta gtaataaaac tggacataca caggcaacat 75120
gtcattaatt ctcaaacttt aacaaatcat atataaccta atataatggt tctcaagtct 75180
gtacatcacg tcacctgtat gaaaaatatg aggaaacaga gacttctttt acactattgg 75240
tgaggtggat aaattgatag agtctttctg gagagaatct ggcaatgcta atcaaaattt 75300
aaaatgcaca tacactttgt tccagcagtt ctatctctag taatttattt ttgccctcat 75360
atatccataa gacatgcaaa taattatatg tgaagatttt ttttttttct ttttctgcag 75420
agacagggtt ttaccatgtt gcccagggtg atctggaact cctgagctca ggtaatccac 75480
ccacctcagc ctcccaaagt gctgggatta caggtgtgag ccatcatgcc tgaccaggat 75540
tttttttttt ttcagcatta tttcttttgt tgttgttgct gttgttttga gagatggagt 75600
ctcactctgt cacccagact ggagtgcagt ggtgcgatct cggctccctg taacctccac 75660
ctcctgggtt caagtgattc tactgcctca gctttccaag cagctgggac tataggcgtg 75720
cgccaccaca cccagctaat ttttgtattt ttagtagaga cggggtttca ccatatgttg 75780
gccaggctgg tcttgaactc ctgacctcag gtgatctgcc cacctcggcc tcccaaagtg 75840
ctgagattat aggcgtgaac caccatgcct ggccatagca ttatttctaa tagtgaaaaa 75900
ttggaaacat gctaagtgtc tatcaatata gcatgagtta gatttatgat gtcaccattc 75960
aattgaaaca ctacatatct cccaaaaaga atggtgttcc aatatggaaa gatatctaag 76020
atttattaag agaaaaagca cattgcagaa cactgggatc ctatttgctt ttttttttct 76080
ttttttgaga cagagtcttg ctctgtcaca ctgcaacctc cgcctcccgg gttcaagcga 76140
ttctcctgcc tcagcctcct gagtagctgc caccatgccc agctaatttt tgtgttttta 76200
gtagagaagg ggtttcacca tgtttgtcag gctggtcttg aactcctgaa ctcgtgatcc 76260
acctgcctca gcctcccaaa gtgctgcgat tactggcatg agccaccgca cctggccatg 76320
aaattttttt ttttttttaa agagctgttc atattcttat tgcctagaag atgtctgaaa 76380
ttacacccaa gaaactcttt ttgagacgga gtcttgctct gttgtccagg ctggagtgca 76440
atggcgtgat cttggctcac tgaaacctct gccttccagg ttcaagcgat tctcctgctt 76500
cagccttctg agtagctggg actacaagcg cccgccacca catctggcta attttttgta 76560
tttttagtag agacagggtt tcaacatgtt ggccaggctg gtcccgaact cctaatctca 76620
ggtgatccac ccaccttggc ctctcaaagt gctgggatta caggcatgag ccactgcgcc 76680
cggctgaaac tctttttttt tcttttaaga tggagtctcg ctctgtcgcc cagacttgag 76740
tgcagtggtg tgatctcagc tcactgcaag ctctgcctcc cgggttcaca ccattctcct 76800
gccctagcct cccaagtagc tgggactaca ggctcccgcc accacacctg gctaattttt 76860
tgtattttta gtagagacag ggtttcacca tgttagccag catggtctca atctcctgac 76920
ttcgtgatcc tcctgcctcg gcctcccaaa gtgctgggat accaggcatg agccaccgtg 76980
cccggccaga actcttaata gtagttattt atgcacgctg ggattggaag acatttactt 77040
tttactggat gtctttccgt attgtgtgct tttttttttt tttttttatg tagggcatac 77100
attacttaag taattttaaa gcctccataa gtaagtgtga tttcctgccc atgtgtttgg 77160
caaaaggaat tgcattggtg gtagacttac attatagtct tacctggagt agcacaggag 77220
gacccaaggt taataggtga acttcgaggc aagccttagc attgaggttg ccatcagcat 77280
tgcttggttg atgtgttcat tcttctggga tggattacaa cctttactgg actttatact 77340
tttcaccagt aaggctttaa aaaaggagtt gaaacattag agaataatta tccaggcagt 77400
aatattcact ggtaaatagt cttccagcct gtggcccaat tggttgattc ttttacgtta 77460
aagaatgcag cctcagctgc tctgcctatg gagtaggatt cttttattta ctttcttaat 77520
aaacttgctt gcccctggct cccccccacc aaaaaaagaa ggcagcctcc cttttgcgaa 77580
tggtaatttc ctatagtttc ctcgtagaat tgtggagtta cctatgctga ggttataggt 77640
tagggtattg agatccagag ttgccacttc tgaggtgtca caactgctaa tggtaaaacc 77700
atttctaaag cccagttctt gtgactttgt ccagtgattg cctgttcacc gtttcatgct 77760
gccttcccat ttgagcattc ccaggaggaa ggggaggttg ccagggacct agtaccatag 77820
tccgaccttg gaatcgttga atatgaggga aagcgttggc ttctcccttc tttctcccaa 77880
acattggaag tatttttggc tgttaaaaag caccccttgt tccatgtgga atcccttgtt 77940
taaaagaagt aaaatatgta cctcctgtcc tccacagacc tgaggaccag tgtgatctca 78000
agaaggttac aggtaaatgt agatgtctct aactgaaagg tggcttttac aggttagaga 78060
aaagagagaa ccctgatctg aaggctattt tatgaagtaa ttaaaatgtt ctaaacttta 78120
aaaataactg ctcaaataat tgtgttgtat agttacttat caactggagg ggctgataag 78180
tatttttcta aaacattttt aaggaaattt tttcctattt tctaatttgc taattttgct 78240
caagtagttt gttagatatt gttaatatag atgttggtta taactgaatg aaagggaaca 78300
actactttga cattttgaaa aacaagcttc attttcttct agtctaatgg atgggatccc 78360
aatgatatgt ttcgatataa tgaagaaaat tatggtgtag tgtctacgta tgatagcagt 78420
ttatcttcgt atacgtaagt ttgaaaagtt tgtttttatt ttagtgcatt tgtctttgat 78480
tttcatcagc ttaatttatg atgaataaat gtttgttagt ttttaagtta aacaattaca 78540
tgaaataatt tttctcttat taccaactgt gataaatttc cattaaaaaa agggaataaa 78600
tgtagtttgc ctataccctg tttttatgct ctaaacaaat tttggttttg tctttttttt 78660
tcttttgaga gggaatctcg ctgtgtctcc aggctggagt gcagtggtgc aatctcggct 78720
cactgcaacc tctgcatccc gggttcaagc gattctcctg cctcagcctc ccgagtagct 78780
gggactatag gcgcgtgcta ccatgcccat ctaatttctg tatttttagt agagacgggg 78840
tttcaccatg ttggccagga tagtctcgat ctcttcacct cgtgatccac ctgcctcggc 78900
ctcccaaagt gctgggatta caggtgtgag ccactgtgcc tggccggttt tgtcttctaa 78960
gttgttaaaa aatatctaaa tttgcaaggg cagagattat ggtgaacagt ttaaccagtt 79020
tttgaaatat gttcctctgg agaaaaggta acagaaaaaa aagttagaat tttgatttat 79080
aaatacacag atcactataa cttttagttt tagttttagt tttagtttct gtttttacca 79140
gtattctaaa ctctaaactt tcttagtagt tgattatgac agatacataa actgtggctt 79200
taaaggactc attttgcttt tcttttcctc atgtttcaga gtgcccttag aaagagataa 79260
ctcagaagaa tttttaaaac gggaagcaag ggcaaaccag ttagcagaag aaattgagtc 79320
aagtgcccag tacaaagctc gagtggccct ggaaaatgat gataggagtg aggaagaaaa 79380
atacacagca gttcagagaa attccagtga acgtgagggg cacagcataa acactaggta 79440
tttaaaggaa atcatgatgc agtattttgg atacacaact caaggtctgt gtgagacggt 79500
gtattgttat tatatttcct cttcctttaa tatagcttag gtagagaatg caagtagaat 79560
tggtttaaga tctgttagag aaaaggttat ggtgatcttg gaaaatatgc ttttgagagt 79620
aagctctgtg gagccaagtg ttggtatatc acggtgagca atccaagatc ttgaagagct 79680
tgttaaaata gttatctggt gggggacacg tgtaacaatc acagcagtac aatatgattt 79740
gcttggttaa aggcatgttc aaagtactag gaacatacag aatgaggagg agctagcata 79800
acctgtagag tcagagaaaa cctcattgag gaggtgacat tttgtgataa gataataggg 79860
tctttgacac ttagagaaga gttgggagaa gagtttatca cctgatgaaa agccatgtac 79920
aagcatggct atgagaaaat ttggccagct caggagaggg ctggttgttg catgtgtctg 79980
gaacacagga tctgtgtcag gtgcagcagt ggcagttgat agtaggaact gaggtcatta 80040
aaggacttgg catgtcatgc taaagagcac cctgttggaa ggagatgggg tgaataaacc 80100
ctggggcatt gaggactggc tgagacacag agaacagtta gtgcactgaa atagttcaac 80160
tgtgagaatt tggtaaccac ctagttaagg gatgagcctg aggtttattt gataactaag 80220
tgacttaatg gatgtactgg taagagagag aggaaacatg gagcaagttt gaggggaaaa 80280
acagtgactc cgtttgtgca gctaattgca tatgtgggct tgtgggtctt tcatttattc 80340
ataaacgtgt tgagaaatac ctgctaccta tctagtaaag taagagatgc atcctctctt 80400
aaaggcagtc agcttagagt ctggtgattt gaattgacat gtccactgat agatgttgac 80460
actgtgagac tggcggttca gtttgaggtt tcatcagcat tgccgatatt ggagccatga 80520
aaaaccaaag aacagccagt gagagaagag atctcagaga aaataaaatt gagaaagtga 80580
aggacaaaaa atgttgtgaa gatagaccaa gattgatgga atcagccata gagaggtcaa 80640
gtgggatgag aatgagcacg catctgttaa actttgtgct taggagcaga atctaaggga 80700
agggacagtc cagaggttag aactcagggt aagatggaag aacaggggca tctgggagtg 80760
aggcagtttg gtttagtgta gaaccttttt gtaacaagca ttcccttctg tctagatgac 80820
ttttagatat gtttcattgg cttggtacct tttagaataa aatgatttag aggatctctc 80880
attttcaggg aaaataaata tattcctcct ggacaaagaa atagagaagt catatcctgg 80940
ggaagtggga gacagaattc accgcgtatg ggccagcctg gatcgggctc catgccatca 81000
agatccactt ctcacacttc agatttcaac ccgaattctg gttcagacca aagagtagtt 81060
aatggaggca agtattttga ccagacttgt caatatcatt gataaaatag ttttctaaat 81120
acttaaaata cttaaaatag tttacataac tgatatgaat gtgcacttta atgatttggt 81180
gagtagcttt cacttcagca ttacttaaaa ttggcttttg tggatattaa attagtaaaa 81240
cattgtatat gtcattgaca tatatattat ttagcatgat gaaatattca tgatgtacta 81300
agataaagtg ctacatttaa cccaagacaa tcacttggcc aaaaacactt cacatataaa 81360
gaaattggaa actttgggta ggttctcaat tttaaaaaca ctggataata aaatttttta 81420
gacataattt atatggaaaa ttctaaccta tgtgcaacac tgtggttaat atagatcaat 81480
tttcattatt tgtttctata ttatgcttac ttcaagaaag gatctgaggt aacttataat 81540
acaagacatg atcaagagtc atgtgaagaa agtgactaga gaaatttgct taaaaaacaa 81600
caaaaacaac ccttagtcta agggtggatg ttacagttta gcaacttaag taaaagaaac 81660
ctgaatcttt agtaggaaga cattttttac tctacctcta aatctaggtt gaatatatct 81720
tgtaggttgt ggatcttttc cataaatcag ggatactgaa caacagttct atggatggta 81780
tggaaatagt aatagcaata gtatgttact aactttgtgg gaaaagagtg gacattcaat 81840
tttagctatt taaatttgga aagttagatg aaaatagaga acactaagtt tccaatttca 81900
tttgttttca ttgagtcttt tctccagaat tcctctccaa atggacactc ttgagtattt 81960
tcagtactta atattggggg tgaaatttct ttgctcactg aggaaagatt ttagttgttt 82020
ataaacagaa ttttaaagtt aaaaaacctg aagggggctg agaaatatat gatacttaag 82080
tgtgtggaac cctatggaga ggagacctgg actgtttgat aagattaagg taagtgatat 82140
gtaatgttaa atactagctg tatctttacc taggcatatc catcagtata aatttatttg 82200
gtgatgactg ctttgtagtt gcagtattta ttaagcagtc gcttagataa gtgtttaact 82260
gtataaatta tttagaaggt ctcccttttt ctagtttaat gaggtcaaga cttttttttt 82320
gaaatagcaa tgaatattat catttgatac tcacaggagt cacaaactct agaagagtaa 82380
tgttttattt ctacttaaat gggacttgct taataagatt ccaaactgag ttctgggttc 82440
aagtgtaaac ctgatgaaaa tcatagataa ttgtaaggaa ccagcatttc taattggata 82500
taatagctac tgcttatttt cgttatgcct cagagttaaa actaatacag taaataatct 82560
tactcctgag taggaattat tgtgatttat tatgtgaaat tatctagtgt atgttatatt 82620
cctttaaaca accagttact gagaaacagt tatagaagca ggattaatag gcaaagtctt 82680
aactgtcttc ttcaatagtg tgtatagatc ctaattaacc ctttgggaac gtgtattcat 82740
ttaaacagac ttaatcttaa ggaggttaaa gtaaaatgtg aatttatgtc agttaagtta 82800
tgctaaaact tatcacaaat caaatgactg tcctcaaagg gttaaaatgt acaagaaatc 82860
atttttgtca ttttactttt tttctgttta cttttttccc tcattttttt ctttagtttt 82920
tatactttcc ttcatatcat ttgttctgtc aggtgttccc tggccatcgc cttgcccatc 82980
tccttcctct cgcccacctt ctcgctacca gtcaggtccc aactctcttc cacctcgggc 83040
agccacccct acacggccgc cctccaggcc cccctcgcgg ccatccagac ccccgtctca 83100
cccctctgct catggttctc cagctcctgt ctctactatg cctaaacgca tgtcttcaga 83160
aggtacaata ccacaatttg ttcatgtttt tgtttgtctt tgtttaactc ctatgtgagt 83220
ttataattac aaaatagttt cctcttcatt atttaataac ctataatttc tgtgttttaa 83280
ctttagttta ttaaaactat ttctattaac cttttgttca ttagagagaa atttgataaa 83340
tgtgtgaagc tataaactct cttgaattgt tgttaaaaag ggggtttatc tctgcctgat 83400
aattatgctt ctttacagcc ccagaagggt ctgccccaca gccttccccc tccttatttg 83460
cactgtatac agtagttaaa caaatgaact ttcttcagcc agtcttgaac ttaggttcat 83520
tttacagctc tttggccaag gtcctagtga accttcctat tggccataag cagggatggt 83580
gttttctggg tcttttttga gagcgacagc ccatgtagct gactttgcgt gtctgccctt 83640
agattaaagt agttgatttt tagaatgcca gaagaattct aaatttaact gagtaatttt 83700
tttaaagtta gctttgcaat cttacatagt gaaaggctgc tttaatctgg aagaagtcct 83760
tgatctgaga taaaattgat aaaaacgaca tatgaatttg aatatttagc tatttctttc 83820
ctcgtcaaaa ataagaataa aatcttgtaa ttcttattca gtatttggcg ctaaatccat 83880
cattgccaca tatcaaatac agggatatgt tgtagaaagg taacattcta atttaaatgc 83940
cacccatata ttaaaaacct gttttctgaa tcataatgtc cttttgatac tagttctgaa 84000
tatttgtgtt aaaattttaa tctgatttgt tcattaaaat tagttaatat tgcttatgtt 84060
gggactaata aagttttccg cacaaaatgt gtttctcctg cttccctgga gaaaactgta 84120
ttggctactt ttaaataaat tgttaccatc taagcaggca ggtcatatga ctttgactga 84180
agcatctaac cttgaagagc aagttccact gattttcaag gtgacttctt tgctcaaaag 84240
ggccttaata gtggtcacta aatgcaaaat tctgttgata tttttcttgt agtccatcat 84300
ttgagtaagc gatgtttatt taatgagaat atattaaata aaacatgatc attaatgact 84360
gtgaacatct ttattacatt aagatttaag gactgctcat gtattaactt cacacagaaa 84420
tatactttct gtgtcattca gagatgttga atatttccat ttgaaaatta tagtgtataa 84480
cattagcatt cttctaaaga tcatgttcgt gtttaaattc ctgttggaag ccaggcatgg 84540
tggctaacgc ctgtaatctc agcactttgg gaggctgagg caggtggatc acttgaggtc 84600
aggagtttga gaccagcctg gccaacatgg tgaaacctcg tctctactaa aaatacccag 84660
ctacttggga ggctgaggca ggagaatcac ttgaacctgg gaggcagagg ttgcagtgag 84720
ttgagatcgt accactgcac tccagcctgg gcgacagaga cagactctgt cttataaaaa 84780
taaaaataaa ataataattc tattggcaac atatattaat ttgaagttct aaagagtttg 84840
gcagccgggt gagagagtga ggagatttgg ctttgacatt agggaagttt tcgcttggtg 84900
ttaacaccag taggcttctc tgatgagggc cattctgtcc actcttttac ctgatagatt 84960
ggtctaatgc acagtagact gatttagaaa gagtagtcac tagtggcatg gcagaatcaa 85020
taatgtagaa ttttgacaat tcatatagtg ctgatttctc ccccaaatgt cagttatttt 85080
ggtcatctat taatagacta atacaagtca tccctttaat agaattttca gctcacagcc 85140
tgctaagcct aagaaactgc ttacaggtta ctgcttactg ttttaagccg agttttaaaa 85200
ttgatgatca tgatagaaga gataaataaa ctaaaatttt agagaaattt aagaagggta 85260
tgtacatatg ttttagtggt atcggggtgt atagggatta atagtcttct gtttaaattt 85320
tttttttcta attttagaag taatgtagaa aattcgggtc agggaaaggt aaaatatatg 85380
gaaagttaaa aatattttat catgtagtca taatttctag taacatattt ctttacaaat 85440
aagacatagt tgaaacagat tgctacagtt cttttaagag ttgacatctt attgttgatt 85500
tcttaccacc aacttcatcc ctccctttct ttaaaaataa agggaaataa taaaatttat 85560
ttataaaact ttgtggcatt ccacaaaata attctgaaag aattagtatg gccaaaaaaa 85620
tatgtatggt gttttttttt tttctatttt taaccaagga aaaactgtag agtgagtgag 85680
tgtgtgtgca tgtgtgtgtg aatgggtgta tttagcagaa aagtagtact gatgaatatc 85740
atggaattta tgtgatgttc actgtttctt ccttagggcc tccaaggatg tccccaaagg 85800
cccagcgaca tcctcgaaat cacagagttt ctgctgggag gggttccata tccagtggcc 85860
tagaatttgt atcccacaac ccacccagtg aagcagctac tcctccagta gcaaggacca 85920
gtccctcggg gggaacgtgg tcatcagtgg tcagtggggg taggtaacac ttgggcataa 85980
tgatggtact cattttgtca ttacactaga tataaagagg gctgagctac aactctgttt 86040
gaggaagtgt aagtatgtat atgttaaaaa tagtagaatc accaggaatt gggaaaccca 86100
tatttttatt ctgggctcta ccacttattc atcatatatt aaagcaagtc agacactcat 86160
tctgaagttg agatttcgca gtgagtaaag tgttaataat tcttgcctag tctacattat 86220
gggattgtga tgagattcct ataaggttca taaatacaga tatattgtaa aactataaag 86280
ttttgtaaag tacctctcta atatgaggca aacacagtat gtaacactat ttggagggac 86340
cgtatttcct tatcttttta gcagctttgt ttatcagtac attctataaa catttatttt 86400
tggcttacat tgtagtgtgt ttctatagca tctgtatatg gcactaattc ccaactatat 86460
ttccataata aggaatatca aatacaaata aagggtccaa gttttatttg tgattagcat 86520
aaggaatatg ctgacagcag ctataaaagt ataaaaatta ggctgggtgt ggtggctcac 86580
gcctgtaatc ccagcacttt gggaggctga ggtgggcgga tcacaaggtc aggagatcga 86640
gaccatcctg gctaacacgg tgaaaccccg tccctactaa aagtacaaaa aaaattagcc 86700
gggcatggtg gcgggtgcct gtagtcccag ctacttggga ggctgaggca ggagaatggc 86760
atgaactcgg gaagcggagc ttgcagttag ctgagatcac gccattgcac tccagcatgg 86820
gcaacagagc aagactctgt ctcaaaaaaa aaaaaaaaaa aaaagtttaa aaactagacg 86880
ttgacatgat tttacaataa ggctgactgc ttttgctact ttgccaatca gtccttagtg 86940
ctttgttccc ataactgtgg taagcaagag cttacaaaga atacttaaaa caaacaaaca 87000
aacaaacaaa aaaaacactt tttctctttt aatcagtcca gagaaccttt aaaagaaaca 87060
agatcggcca gttgctgtgg ctcatgcctg taatcccagc actttgggag gctgaggtgg 87120
gtggatcact tgaggtcagg agttcaagac tggcctgacc aacatgatga aaccccatct 87180
ctactaaaaa tacaaaatta gctgagtgtg gtggctattt gagaggctga ggcaggagaa 87240
tcatttgaac ccaggaggtg aaggttgcag tgagccaaga tcacaccatt gcactccagt 87300
ctgggtgaca agagcgaaac tctatctcaa aaaaaagaaa aaagaaacaa gatcttcaag 87360
cttaaggaaa caaaaacaaa actcagctgt gttaaatctg tttttagttg ctatacattt 87420
ctgctcagct tcatgtgatg cacattcatg taattgtatc ctaaattcct ttgtactttt 87480
tattttcttc cttggtcttc aattatctta agactaccaa gaaaacaaaa attttaaaaa 87540
tcttcttcag ccggtcaggc gcagtggctc acggctgtaa tcccagcact tggggaggct 87600
gaggcgggtg gatcacgagg tcaggagttc aacaccagcc tggccaacat ggtgaaacgt 87660
cgtctctact aaaaatacaa aaattagctg ggcattgtgg cgcgttcttg taatcccagc 87720
tgctcaggag gctgaggcag gagaattgct tgaaccagga cccgggaggt gtaggttgcg 87780
gtgagcggag atcgcgccac tgcactccag cctgggctat agagtgagac tccatttcaa 87840
aaaaaaaaaa aaaaatctgc ttcagctatt ctgttaatct tttgacatta cttagatggt 87900
ctggaaataa attttgagaa taacatgatt agaagtgaga gagtataagc atagttttgg 87960
agatacactc agaatagcat tatagatttt ctctttttac taattggaaa aatggcagtt 88020
gttgaataat agttttcttc cgtgaccctt gtgacttaaa aaaaaaaaaa cactgaaatg 88080
aaataatcga accattttct ctaaaccttt gaatctgagc tctgcagtta ggtttataat 88140
ggtatatgaa acctattaga tatatacttg gaagtcatat gggatacaaa ccctgctttt 88200
attatcttcc ccttttgact aacttgggtc tcaagtttcc ttaattactg cacagtggac 88260
cttgatgttg ctataaagaa tgtgtagggc tgggcatggt ggctcatgcc tgtaatccca 88320
gcactttggg aggccaaggt aggcagatca cctgaggtca ggagtttgag accagcctgg 88380
ccagcatggt gaaaccccgt ctctactaaa aatacaaaaa aattagctgg ttgtggtggc 88440
gagtgccttt aatcccagct actccagagg ctgaggcagg agaatcactt gatacattta 88500
gttaggagag aaaatcatac ttatgttagt aattgctgct gttcttcata tacttgtggt 88560
tttgattgcc agcaaattcc taacattttg gaaaagaaaa cagtaatggg ataaagggta 88620
agggctagag aggacagttt tatttaccta gatcttcaga gaagcctgaa gcctctttta 88680
ggaagtaaca tttgaactga gaatgtaata aatacatttt ccctttcttc tagttccaag 88740
attatcccct aaaactcata gacccaggtc tcccagacag aacagtattg gaaatacccc 88800
cagtgggcca gttcttgctt ctccccaagc tggtattatt ccaactgaag ctgttgccat 88860
gcctattcca gctgcatctc ctacgcctgc tagtcctgca tcgaacagag ctgttacccc 88920
ttctagtgag ggtatgtaac aaagggcttc tggatccata atctcagctg tgaaattgaa 88980
tgttagaggg tgatattata tgaaaaaatt ctaggttatt tttattcata gacaagtatt 89040
tttagtgcac atttaaaagt ttatgtaaat tttgatgttg tttaatacta ctaatttaat 89100
atagtgtctg tgttacaaag gttaacattc ctgggtgtca aatacctaca taaataaaat 89160
tattggtgtt tcatatgaca tctgcaaagg aaaaaaagcc tctgtttaaa tgaaagcatt 89220
attttccaaa aacataggaa atcaaaatta ttgttcagtg ttttcttgtt ttgcttttct 89280
aacttatctg aatttttttt aaaaaattgt tttctagcta aagattccag gcttcaagat 89340
cagaggcaga actctcctgc agggaataaa gaaaatatta aacccaatga aacatcacct 89400
agcttctcaa aagctgaaaa caaaggttag agtttaaaga gtcattaagc ttaactgtag 89460
gaataggaag aagtatgtct aatttcatgc ccatacagaa tatttttgtt caacatttct 89520
tcttactatt gtgatagata aatgtattgc ttgacaaatt ccaaaatcca aatttaatat 89580
ttgaaattat tttctgatct tatatcttat tctaatttct atcatctcat actaaaaaga 89640
atgtgatgtt aaagtttaaa aataaacctg tgtcttaaca gttcttaatt ttacaggtat 89700
atcaccagtt gtttctgaac atagaaaaca gattgatgat ttaaagaaat ttaagaatga 89760
ttttagggta agtattgtac taactgatga atttgagttt tagaaaataa gcattactaa 89820
agatttatct atttataaaa atgcgttatg tatacagtca gaaacatcaa accatatatg 89880
tagaaagcag aacattttta aagtggtctt tgcctatcct ttaagtggga taactaaaat 89940
catgagattt ggtaacaaca atatgtaggt atcaaatgag agtatagccc tgacatttga 90000
aaccaccata gcacagctta ctatttgatg gtcatttgta ctttgttcag tgaagctaga 90060
tattagtaga gcaaggccaa gtcattaata atctagtgtg gcaaatggaa gatgtactgg 90120
actctggtgt tctgaggtag ttggagattt atactttgta cacaaatata ttgtggtcaa 90180
aatctttctg taacattatt tctctgtctt agcacaggct ttacttaaca tctctccttg 90240
attgtcattt cattcttttg catgttattt actataggta tcgaggtaga ttttgagacc 90300
aaccaataaa tcttcttgaa acttagcttc ttagaaagga aaatctaaat accagccttt 90360
taaaaaaagt agctgaatta aaggatgagt gaaccaaagg caaaggtagc ctttcctcag 90420
cctgtgtttt agctttctaa atgttaacaa tagcttcatt cttgacttat tggtaacatt 90480
caaaatacta cttattattt catactttag cacatgtatc tattcagctt taatgctatt 90540
aacagttgtt aacctaagtt ttcatttgtt ggcgggcacg gtggctcaca cctgtaatcc 90600
tagcactttg ggaggccgag gtgggcagat cacctaaggt caggagttcg agaccagcct 90660
ggtcaacatg gtgaaaccct gtcttgacca aaaatagaaa aattagctag gcatggtggc 90720
gcacacttgt aatcccagct acttggcagg ctgaggcagg ataatcgctt gaacccagga 90780
gacagaggtt gcagtgagcc gagatcacac cactccactc catcctgggc gacagagcaa 90840
gactgcatct caaaaaaaaa aaaaaaaaaa aaaagttttt caatttgtta aacaatagtt 90900
aacacataca aatgatacaa agaatattga atatgatcat gtgcccacta cccagcttag 90960
taaataaagc attctaacac agttaaactc ctcttatgta tctgcccctc ctcagctgct 91020
tccccctgtt tccttccaaa aggaagggtt tcttttctgt gcagttcttt atatttatac 91080
tgcatatgaa tatatctgtg agcaatagat gatattttgc ataatcttaa atttgctata 91140
aagtcttttt ttttttttta attgatcatt cttgggtgtt tctcgcagag ggggatttgg 91200
cagggtcata ggacaatagt ggagggaagg tcagcagata aaaagtgaac aaaggtctct 91260
ggttttccta ggcagaggac cctgcggcct tccgcagtgt ttgtgtccct gggtacttga 91320
gattagggag tggtgatgac tcttaacgag catgctgcct tcaagcatct gtttaacaaa 91380
gcacatcttg caccgccctt aatccattta accctgagtg acacagcaca tgtttcagag 91440
agcacagggt tgggggtaag gtcatagatc aacaggatcc caaggcagaa gaatctttct 91500
tagtacagaa caaaatgaaa agtctaccat gtctacttct ttctccacag acgcagcaac 91560
catccgattt ctcaatcttt tccccacctt tccccctttt ctattccaca aagccgccat 91620
tgtcatcatg gcccgttctc aataagctgt tgggtacacc tcccagacgg ggtggtggcc 91680
gggcagaggg gctcctcact tcccagaagg ggcggccggg cagaggtgcc ccccacctcc 91740
cggacggggc ggctggctgg gcgggggctg accccccacc tccctcccgg atggggcggc 91800
tggccgggcg ggggctgacc cccacctccc tcccggacgg gttggctgcc gggtggagat 91860
gctcctcact tcccagacgg ggtggctgcc aggcggaggg gcttctcact tctcagacgg 91920
ggcggctgcc gggcagaggg gctcctcact tctcagacgg ggcggccagg cagagacgct 91980
cctcacctcc cagacggggt cgcggccggg cagaggcgct cctcacatcc cagacggggc 92040
agcggggcag aggcgctccc cacatctcag acgacgggtg gccgggcaga gacgctcctc 92100
acttcctaga cgggatggcg gccgggaaga ggtgctcctc acttcccaga ctgggcagcc 92160
gggcagaggg gctcctcaca tcccagacga tgggtggcca ggcagagacg ctcctcactt 92220
cccagacggg gtggcggccg ggcagaggct gcaatctcgg cactttggga ggccaaggca 92280
ggtggctggg aggtggaggt tgtagcgagc cgagatcacg ccactgcact ccagcctggg 92340
caccattgag cactgagtga acgagactcc gtctgcaatc ccggcacctc gggaggccga 92400
ggctggcaga tcactcgcgg ttaggagctg gagaccagcc cggccaacac agcgaaaccc 92460
cgtctccacc aaaaaaatac gaaaaccagt caggcgtggc ggcgcgggcc tgcaatcaca 92520
ggcactaggc aggctgaggc aggagaatca ggcagggagg ttgcagtgag ccgagatggc 92580
agcagtacag tctagcttcg gctcggcatc agagggagac cgtggaaaga gagggagagg 92640
gagaccgtgg ggagaaggag aaggaggggg agggggaggg ggggagaggg agagggacaa 92700
tgatgtcttg ctgtaggtat tcttccccat ttgaattttt tcctcagcat tatttttttt 92760
aacatcattc agtctcctct tatactacac ttggattgaa tttaatatct catgaagaaa 92820
aaacatttct actttgaagc atgtgaatta gcatgttttt ataacagctt tattgagata 92880
taatttacat atataaataa accgtttaaa gtgtataaat cagtggtttt taatgagata 92940
taatttacat atataaatca accatttaaa gtgtataaat cagtggtttt taaaatattc 93000
acaatgttgt acaaccgtct tctcagttga ttttaaaaca tactcttcac ccccaaaaga 93060
aaccccgtgc ccagtttagc agtcgttcca catttgcctc cagcccttct ctttccccta 93120
ctcccaaccc taagcaaccg ttaatctact ttctgtctct atggatgggc ttatttgggg 93180
caaattccat ttcatacaaa tggaataata aaatatgtgg cttttatgac tggcttcttt 93240
cactcagagt agtgttataa aagttcatcc atgttggagc atgtttcagt acttcatttc 93300
tttttgtgac tgactaatat tccttgatgt ggataatacc acattttgtt tatccattaa 93360
tcagtttgta gctatttgtg gtgttctcac tgtttgacta ttctgaataa cactgccaca 93420
aacatgagtg tgcagttttt ttctcgtcct atcttttcat ttcttttgtg tacctaccta 93480
ggagttgaat tgctgggtca tatggcaact gtgtttaacc ttttgaggaa ctaccaagct 93540
atttgccaag atatctacac tattttacat tcccaccagc agggtatgag ggtttctgtt 93600
tctccacatc cttgctaaca cttattgtct tgtctttttt gattatagtc atccttgtgg 93660
gtgtgaagtg ttaacctcat tgtggcttta atgtgcagtt ctttcatggc taatgatgtt 93720
gaacatcttt tgtgtttatt ggccatttat atatcttctt tggattgatg tctgttcaaa 93780
tctttaccca ttttaaaaat tgagttgtct ttttattatt gggttgtggg agttctttat 93840
atattgtgtg tacaagtccc tgttagatac atggtttgca aatgttttct cctgttctgt 93900
tggttgtctt tttacttttt catcccttga agcacaaaaa tttttaattt tgatgaagtc 93960
caatttatct gattttgaag taagcttttg gtgtcgtatc taagaaaata ctgtttcatc 94020
aatcattaag gtttattact cttctgggtt tttttaagaa ttacatttag aggtgtgatc 94080
catttggagc aacttttttt ttcttttgac acagaatctc gctcttttgc ttaggctgga 94140
gggcagtggt gcaatcttgg ctcacagcag cctcagcctc ctgggctcaa atgagtagct 94200
ggtactacag gtgtgcacca ccacaccttg ctattaataa cttttgtatt tttttgtaga 94260
gacagaattt cgccatgttg cccaggctgg tctcaaacac ttggactcaa gtgacacgcc 94320
cacctcagcc tcccaaagtg aaaaattgct ttcaccttgc actgcggact cgccctgaat 94380
tctttcttgt gcaagatcca agagccctct ctgggggtct ggatcgggac ccctttccta 94440
taacaatatt atgagaataa catttgattt tttttaagtg aaacaaattg ttattaaaaa 94500
attaaaaaag gtcataggag agtgacttgg tgctcagccc attttgagca gttatttaat 94560
atagcataag gtggggttca aattcattct ttatattaat tttttatttc taattgacac 94620
ataaccatac acttataacc atttttactg tgtaagttca gattcattct tccgtatgta 94680
ggtattagtt gtcccagcac catctgttaa aaagactatt cttggccagg cacagtggct 94740
ctcaacgcct gtaatcccag cactttggga gtcccaagca ggcagatcac atgaggtcag 94800
gagttcgaaa ccagtctgac caaatggtga aaccgcatgt ctactaaaaa tacaaaaatt 94860
acctgggtgt ggtggcgcac acctgtagtc tagtcccact actgtagtgg ctgaggcagg 94920
agattcgctt gaacccagga ggtagaggtt gcagtgagct gagatcatgc actccagtgt 94980
gggcgacaga gtgagactcc atctcaaaaa aaagactatt ctttcctcca ttgaattatc 95040
ttcacatgct tgttggaagt ctgttgacta caaatgtgaa agtttattac tggactctga 95100
attgtcctcc actgaatctc tatgtcttat ccttatggca gtaccatact gtcttgatta 95160
gagttactgt attttaaaag gctgtacttt ttcagttagc agaaaacatt ttagctatca 95220
gcacaacttt ctgtaaacct tcattaatgc ttgacttaaa ttccaagaag gagcaacata 95280
aaaagtctta tctctttagg agttttagtc ttactacttt taggtgcctg aataaccaaa 95340
tgtattattt agcctcttac taataactcc ttgatccata ggggcatacc aggaagaaaa 95400
gaagtggttt ttaaaaaatg agagtgggcc gggcacggtg gctgatacct ataatcctaa 95460
cactttggga ggctgaggcg ggtggatcac ttgaggtcag gagtttgaga ccagcctgga 95520
taacatggcg aaaccctatc tttattaaaa atatataaat tagccgggca tggtggcaca 95580
tgcctgtaat cccagctact caggaggctg aggcaggaga atcacttgaa tccaggaggt 95640
ggaggttgca gtgatccgag attgcatcag tgggcgacag agcgagaatc tgtctcaaag 95700
aaaaaaaaag agagtggaaa aaaaaaatat gtgtcccaga acttaaattt taattaaaaa 95760
aaaataaaag agtgaacttt ctaattgttc tcttcagata atataatgtt attctcttat 95820
gttttattgc gtatttcctg tgtaccagat gctgttcttc atgcttgtat gttaaatctt 95880
gtctaacatc tctgtcaagc aagttctgtt tgtatctgca ctgtgtatat taggcagctt 95940
gggcaaagag aagttaagta atctgcccaa actcacatgg ctagtaagta agagggctga 96000
ccatctggtg tttaagcttc tagcagtgct ttgaatagta actaatgcat agtgcatgct 96060
gcactgtcag tcagtgattc attagagcta acttcatgac atgctcatag ccccaaactg 96120
catttgttca caaatatctg tagtccttca tttaggcaga aatagaaata ccttgtgtgt 96180
ttgttgttcc ttcccttttg agccatatgc agagtgctga tagctttatt tgtgtaagaa 96240
ttgctagtaa tttgatctgt tttgggttaa taatgtgggt tttagaggta aatggaccta 96300
ggtttgaatg ttggcctcta tacatcatgt gcgtaacatt gtggcatgct atctacttcc 96360
cccaagccaa aatgggttaa ttttagaacc tgcttcatag tgttcctgtg agagctcgat 96420
gagatattgc ctataaagtg tttagcatag tgcctagcac atggtatgta ttcaatacat 96480
gttcattctt actagcaaaa tatagatgac ccagtattgt acagagtatg tacaatggtg 96540
tcattgtacc atttcatgtg gagtcacata agaatttcag ttttctgctg ggcatgatgg 96600
ctcactcctg taatcccagc actttgggag gctgaggtgg atggatcagc tgaggtcagg 96660
agttccagac cagcctggcc gacatgatga aaccccatct ctactaaaaa tacaaaaaat 96720
tagccaggcg tggtggcagg tgcctgtaat cccagctact cgcaagactg aggcaggaga 96780
aatgcttgaa cccgggaggc ggtggttgcc atgagttaag atcgtgccgc tgcactccag 96840
cctgggcaat aagagcgaaa ctccgtctcc aaaaaaaaga aaaaaaaaga acttaagttt 96900
tccattagat ttagtatagt gcagagagga aatacagcag agtgctatat tccatatata 96960
gcaatatagc attagaacaa tatattccaa tacagcagag tgctatattc agataccaac 97020
tagtggactt gctatttgta agatggcaat aatagtatct acatcaaata gggctgttgt 97080
gaagactaaa tgaataagtc tataaatagt ttagaacagt gtctggacag gtacagtggc 97140
tcatgcctga atcttagcac tttgggaggc tgagacaggt ggatagcttg agctcaggca 97200
ttaaagacca acctgggtaa catggtaaaa ccctgtttct acaaaaaaat acacacatta 97260
gccaggtgtg gtggcacatg ctaatagtac cagctactca ggaggctgag gtgggagaat 97320
cacttgagcc tgggagatgg aggttgcagt gaggtgagct tgcaccactg cgctccagtc 97380
tgggcaacgg agtcagaccc tgtttggaaa aaaaaaaaaa agtgtccaac ccatagtaag 97440
aaatgcagat gtgtttgaca ttgtaagaaa aagcaacacc aaaagtctga tttttgcctt 97500
cactcaagaa ctcttatgat aattaaactc cgaagtcctt ggcaatatat atagttggtc 97560
tgttatgtgg atcgcctcta ctaaagattt ttgtgaacaa atgaaagttt aagtagtaag 97620
ttcctacatc gtgacttaaa ttgccagtgt gcccacataa ataccctgtc aacatttgcc 97680
cttagccact tgactcttta gctatattgg taatgcagta aagcttgcga tgcgccagag 97740
ttgcataatg ctgtttgcca tgacaccaag agccttggta atgaaaccat tgaaattggt 97800
ttgcctatac tgaggctgaa gaggtatctt ggctctctaa ttttaaggca acctttttgg 97860
ctgtgtaggt ttctctttag cttgtttctc accacctggg gctgtggctt aggtccgttg 97920
tcctaacctg tggcttaggt tctgtttttg ttgcttgtac ttgctccccc ttttttcagc 97980
cattcctgtt ttctttcttt tgtagaggat gccatcttaa atcatcttca gccagtggta 98040
gcattttatt ttttctggtc tgcaaactta aaaacctcat cacttatttt gctaatatct 98100
ttgtcttctg ttctttttga tggtccttgg ttttgcagtc tactttaaag gtttttattt 98160
ttttatgggt acatagtaga cgtattattc atagggtctg tgagatattt agataaaggc 98220
atataatgtg taataatcac attagggtaa atggggtatc catcaccatc atcattcatc 98280
atttctttgt gtaatgaacg ttgcaattgt actccctcag ttattctaaa aagtacaaca 98340
aattaatgct gactgtagtc accctgcttt gttgtcaaat actagatctt attcattctt 98400
tatttaactt tttaaatttt aaacttattt tatttattta tttttagacg gagtctcact 98460
ctgtcgccag gctggagtgc ggtggcgcag tctcaactca ctgcaacctc cgcctccagg 98520
gttcaagtga ttctcctgcc tcagcctcct gactagctgg aactacaggc acgtgccacc 98580
acgcccagct aatttttgta tttttagtag agacggggtt tcactatgtt ggctgggatg 98640
gtcttgatct cttgaccttg tgatccggct gccacagcct cccaaagtgc tggggttgca 98700
ggcgtgagcc accgtgcccg gcctttaaaa ttattttaaa tcattttaat atctttttca 98760
tttctgcctc cggtcctgca gagttcttat tcgttctttc taaattttct ttgcacccac 98820
taatcacctc atttcccttc ttctccccat tacccttccc aacttctggt aaccattctg 98880
ctatctccat gtgttcaatt gtttttattt ttagtgcctg caaacgagta agaatatgca 98940
aagtttatct ttctgtccct ggcttatttt acttaacata atgtcctcca gtgccatcta 99000
cattgctgca aatgacagga tctcattctt ttttatggct gaatggtaat ctattgtgta 99060
tatataccac attttctttc tccatttgtc tgtcagtgga cacgtaggtt gattccaaat 99120
cttggctgtt gtgtatatag tgccgtagta aacatgggag tgcagatatt ccttcaataa 99180
actgatttcc tttctgagta tatacctagc agtgcaattg ctggatcata tggtagctct 99240
atttttagtt ttttgaggaa tttccatact gttctccata gtggttttac caatttacat 99300
gtccaccaac agtgtgtgaa ggttcccctt tatccacatc gttaccagca tttgttattg 99360
cctgtctttt ggataaaagc cattttaact ggggtgagat gatatcttgt tgtagtttta 99420
atttccattt ttctggtgat cagtagtatt gaataccttt catatacctg tttgccattc 99480
ataaataacg atgaggtctt gctgtttggc ccaggctggt ctcgaactcc tgggctcaag 99540
caatcctccc accttggctt cccaaaatgc tgaaattata gttgtgagcc actgcacctg 99600
gccttgtatg tcttcctttt ttttttgttt tgttttgttt ttgagacaga gtctcacttt 99660
gttgcccagg ctggagcgta gtggtgtgat cttggctcac tgcgccctac acctcccgga 99720
ttcaagcaat tctcctgcct cctgccacca tgtctgccta atttttgtat ttttagtaga 99780
gacgggattt ctccttgttg cccaggctgg tcttgaactc ctaacctcag gtgatttacc 99840
tgcctcagcc tcccaaagtg ctaggattac aggcgtgagc tgctgcgccc agcctgtatg 99900
tcgtcttttg agaaatgtct attcagatct tttgcccatt tttaattgag ttactaaaat 99960
tttccctatg gagttgcttg agtgcctttt atattctggt tattgatccc ttgtcagatg 100020
agtagtttgc aaatattttc tcccattctg tgggctgtct cttcactttg ttgatggttt 100080
cctttgctgt gcagaagctt tttaacttga tgtgatccca tttgtccatc tttgctttgg 100140
ttgcctgtac ttttggggta ttactcaaga aatctttgcc cagagtaatg tccctgggag 100200
tttaatgttt tcttttagta gtttcatagt ttgaggtctt agatttaaat ctttagtcca 100260
ttttgatttg attttttttt aatatggtgg gacacagggg tctggtttca ttcttctgca 100320
tatggatatc cagttttccc agcaccattt attgaagaga ctgtcctttc cccagtgtat 100380
gttcatggct tctttgtgga aaatgagttc acttagacgt atggattcat ttctgagttc 100440
tctgttctgt ttcattgatc tatatctttt tttatgccag taccatgcca ttttggttac 100500
aataatttga agtcagataa tgattcctcc cgttttgttc attttgctca gtatggcttt 100560
tgctcttttg ggccttttgt ggttccctac aaattttaga attatttttg tctacttctg 100620
tgaggaatgt cattggtatt ttgataggga ttgcactgaa tctgtagatt gctttgagta 100680
ttatcaacat tttagcaata ttaattcttc taatccataa acatggaatc tcttttcatg 100740
ttttttctgt gtcatcaatt tcagtgtttt aaagttgtca ttatagaaat cttttactca 100800
tttggttaag tttattccta agtattttat tatatttgta gctattgtaa atgggattgc 100860
gtttaaaaaa tttttcagat tgtttgctgt taaatataaa aatgctcctg atttttgtgt 100920
gttgattttt gtatcctgca attttactga atttgtttgt cagttctaat aggtttttct 100980
tttttggagt ctaggttttt ccaaatgtaa gatcatatta tctgcaaaca aggataattt 101040
gacttcttcc attccagtgt ggatgctttt tatttctttc tgttgtctga ttgctccaat 101100
taggacttcc gagtattatg ttgaataaca atggtgaaag tgggcatcct tgtcttgttc 101160
cagatcttag aggaaagcct ttcagttttt cccttttcag tatggtacta gttatgggtc 101220
tgtcatatat ggcttctgtt ttgttgaggt atattccttc tatacccagt tctttggggt 101280
ttttttgttt gtttgttttt gagatggagt ctcactctgt cacccaggct ggagtgcagt 101340
ggcgcaatgt tggctcactg caagctccac ctcctgggtt catgccgttc tcctgcctca 101400
gcctcccgag tagctgggac tacaggtgtc cgctaacacg cccggctaat tttttgtatt 101460
tttagtagag acggggtttc accgtgttag ccaggatggt ctcgaactcc tgacctcatg 101520
atctgcccgt ctcagcctcc caaagtgctg ggattacagg cgtgagccac cacgcccggc 101580
caagggtttt aatcataagg ggatgtggca ttttatgtga tataaattat atatttatat 101640
catgtgatat atatttatat catacacagt ataaataata tatatatata ttttttagtc 101700
tttgtctttt attctgttaa gatgtaccat gtttattgat ttgcgtatgt cgaaccatcc 101760
ttgcatccct gggatgaatc ccacttagtc atgatgaatg atctttttaa tgtgttactg 101820
aattcggttt gctagtatta tattgaggat ttttgcataa tgttcttcag agacactggc 101880
ttctagtttt ccctttttga tgtgtccttt ggttttgtat agggtaatag tggccttgta 101940
gaatgagttt agaagtattc cctcttcctg tattgtgttg gaatagtttg agtaggattg 102000
gtattagttc ttctttaaag gtttagtaga attcagcagt gaagccatca ggtccatggc 102060
ttttctttgc tgggagacta tttcttatag ctttgatctc gttacttgtt attggtctcg 102120
ttacttgtta ttgtatttgg gttttggatt tctttgtggt tcagtcttgg taggttgtat 102180
gtgtctagga atttatccat ttcttcaagg ttttccaatg tatcagcata tagatgctca 102240
tagtagtctc taatgatcct ttgaatttcg gtggtaacaa ttataatgtc tcctttttca 102300
tctctcattt tattatttgg gttttctctt ttttttctga gtctggctaa aggtttgtca 102360
gttttgttta tctcttcaaa acaatttact gttttattga tcttttgtat tttcttcatt 102420
tcaattttat ttatttctgc tttgattttt tttatttctt ctactgattt taggttttgt 102480
ccttgctttt ctagttcttt aggatgtatt ggcagatgaa gtttttccac ttttttgatg 102540
taggcactta ctgctgtaaa cattcctctt attgttgctt ttactgtatc ctataggttt 102600
tgataagctg tgtttccatt ttcatttgtt tcaaggaatt ttccagtttt cttcttaatt 102660
tcttcatgga cccactggtc attcaggagc atattgctta attttcatgt atttgtatac 102720
tttccaaagt tcctcttgtt atctagtgtt attttatttt atttttattt ttgttttttt 102780
gagatggagt ctcgctctgt cacccatgct ggagtgtagt ggcgcgatct cggcttactg 102840
caacctctgc ctccccagtt caagtgattc ttctgcctca gcctcctgag tagctgggat 102900
tacaggcatg taccaccact cctggctaat ttttttttgt atttttagta gagagggggt 102960
ttcaccatgt tggtcaagct gatctcgaac tcctgacctc agatgatcca cccaccttgg 103020
cctcctaaag tgctggaatt acaggcatga gccaccgtgc ccggcctcta gtgttatctt 103080
attgtgatca gagaagatag ttgatatgat tttaactttt ttgaattttt atttatttat 103140
ttgtttgttt gtttgtttgt ttgtaacaga gtctcactct gttacccagg ctggagtaca 103200
tgtcatgatc ttggctcacc tgcaacctcc gccttcctgg ctcaagcaat cctcccacct 103260
tagccttcca agtagctggg actacaggca catgccgtca catatggctg atatttttgg 103320
attttttttt tttttgtaga gatggggctt tgcgatgtgt cccagggttg tttcgaactc 103380
ctgagctcaa gcaatccacc tatttcggcc tcccaaggtg ctgggattac agacatgagc 103440
cactgtgcca cgtcaaatct ttagacttgt tttgtggctt aacatagggt ctatctttga 103500
gagcaatcca tatgttgagg agaagaatgt gtattctata gctgttggac acaatgttct 103560
gtaaatatgt attgggccta tttggtctat agagcaaatt aggtctaatg tttctttgtt 103620
gattttctgt ctgaatgatc tgtccattgc tgagagtggg gtgttgaagt ttccgactgt 103680
tactgaggtc tgtttctctt ttttgctcta ataatgtttg ctttatatat ctggatgctc 103740
cagtattggt tgcatatgta tttatacttg ttataacctc ttgccgaatt gatcccttta 103800
tcattataca ataatcttct ttgtctgttt ttatagactt tgtctcaaaa tctattttat 103860
ctaagcatag ctactcctgt tcttttctgg tttccatttg catggaatat tgttttccag 103920
ctcttcaatt ttagtctatg tgtgatttta taggtaaagt gtgtttcttg taggcaatgg 103980
atctttggtt tttttttttt tttttttgag acagagtttt gctattgttg cccaggctgg 104040
agggcaatgg cgctatctca gctcactgca acctccgcct cctgagttca agcgattctc 104100
ctgcctcagc ctcccaagta gctgggatta caggcgcctg ccaccaagcc cagctaaatt 104160
ttttgtattt tcagtagaga tggggtttca gtatgttcgt caggctgttc ttgaactcct 104220
aacctcaggt gatttgcctg ccttggcctc ccaaagtcct gggattacag gcgtgagcca 104280
ccgcacccag cctttttttt aaatccattt agccactctg tatcttttga ttggagagtt 104340
tagtcgattt acattcagtg ttgttactga ttagtgagga cttaactact accattttgt 104400
tacttattat ctggttgttt tgtagtccta ctccctccct tcccccttct tttttacttc 104460
ctcttcgctc cttttttccc tccctccctt ccttgttttg aaagtgattt tctctggtgg 104520
tatgttttaa tttcctgctt tatatttttt gtgtatctgt tgtaggtgtt tttgatttaa 104580
gatcaccatg acagctgggt gcagtggttc acacctgtaa tcccagcact ttgggaggcc 104640
gaggtgggtg gatcaagagg tcaggagatt gagaccagcc tggctaacat ggtgaaaccc 104700
catctctact aaaaatacaa aacttagcca ggcgtggagg cacgtgcctg taatctcaga 104760
tactcaggag gctgaggcag gagaattgct tgaacccagg aggcagaggt tgcagtgagt 104820
caatattgtg ccactgcacc ccagcctggg cgacagagtg agactccgtc tcaaaaaaaa 104880
aaaaaaaaaa gagatcacat aagggttgca aataacattt tataacccat tattttaaac 104940
caatgacaac ttgaaacttt gattgcaaaa acaagcaagc aaagagaaaa ctaataaaaa 105000
ctctacactt catctgcccg ctttttaact tttgttgttt ttatttatat ctttattata 105060
ctatgtctta aaaaactgta gttataagcc aggcgcagtg gttcacgtgt gtaatcccag 105120
cactttggga ggctgaggtg ggcggatcac ctaaggtcag gagttcgaga ccagcctagc 105180
caatatggca aaaccccctc tctactaaaa atagaaaaat tagccggaca tggtggcggg 105240
tgcctgtaat cccagctact cggaggctga ggcaggagaa tcacttgaac ccaggaggcc 105300
caggttgcag tgagccgaga gtgcgccact gcactccagt ctgggcaaca gagtaagact 105360
gtctcaaaaa acaatacaaa acaaaacaaa accctggcct agtggctcac gcctaatccc 105420
agcactttgg aaggcaaagg tggggcgaat cacaaggtta ggagttcgag accagcctga 105480
ccaacgtggt gaaactctgt ctctactaaa aatacaaaaa ttagccaggc gtggtggcac 105540
gcacctgtaa tcctagctac tcaggaggct gaggcaggag aatcgcttga acctgggagg 105600
cggaggttgc agttagccga gatcgcgcca ctgccgtcca gcctgggcag cagagcaaga 105660
ctctgtctca caaaaaaaaa aaaaattgta gttcttattt ttgaaaggtt cattttttat 105720
tcttcctgct caaaatatga gtagtagttt atacaccaca attacagtgt tacaatattc 105780
tgtatttttc tgtgtacttg ttaccagtga gtttttgcac cttcaggtga tttattattg 105840
tttgttaaca tccttttctt gcagattgaa gaactttttt tttttttttt tttttttgag 105900
acagagtcat gctctgttac cagcctggag tgcagtggtg ccatcttggc tcactacaac 105960
ctccaactcc caggttcaag cgattcttct gcctcagcct cccaagtagc tgggattaca 106020
agcatgtgcc accacgccca gctacttttt gtatttttag taaagacggg gttttgccat 106080
atttgccagg ctggtcttga gctcctgacc tcagggtgat ccgcccgcct tggcatccta 106140
aagtgctagg attataagcg tgagtcatcg tgcccaactt ggttgtttat tttcaaatag 106200
cctgaattca agctcactaa tgttttctgc tgcttgatac atttctgcta ttgagagact 106260
gatgcatttt tcagtttgtc aattgaattt ttccactttg ggatttctgc ttgattcttt 106320
ttactaataa ttattgcagt ctctttttta aatttatagg attctgaatt tgttctctgt 106380
attatcttgg atttcgttga actttctcaa agcattcagc ttgaattctg tctgaaagtt 106440
cacatatctc ttatcacttg ggaattggtc actggtgtcc tttattttta gttcatttgg 106500
tgaggtcatg ttttctcaga tggccttgat gcttgtggat gttcatcagt gtctgggcat 106560
tgaagagttg ggtattctgt tctttgtagt ctggttttgt ttgtacgcat tctttttttt 106620
ttttttctgt ttttgagaca gagtctcgct ctgtcgccca ggctggagtg cagtggcaca 106680
gtctttgctc accgcaacct ccgtctcccg gattcaagca attctcctgc ctcagcctcc 106740
tgagtagctg ggattacagg tgcgtgccac cacgcctggc taatttttgt atttttagta 106800
aatatggtgt ttcaccatgt tggtcaggct ggtctcgaac tcctaacctc gtgatctgtc 106860
cgccttggcc tctcagagtg ttgggattac aggcgttagc cactgcatcc ggctcccatt 106920
cttcttgaga aggtttttca agtattcaaa gggaattaag tgttgtcatc taagtcttcg 106980
ctcactgcag ccatacatgc attagagggc accccaagac tagtaatgtt gtgactctgt 107040
agaggtatca ccttggtagt cttggggaag atctgggaga attccctgta ttaccaggca 107100
gtctcttgtc ctcttacatt tctccaaaca aatggagtct ctctttgtgc tgagctgctt 107160
ggagtttggg gaagggtgac acaagcactg ccatggccac cgtcactgga actgtacttg 107220
gtctcaccca aggcctgtgg cagctatttt ctggccacca ctgatgttaa tttaaggccc 107280
aagggtgctt tagtcagtag gtgaagaatc ctgcaagaac tgggtcttta ctttcagtgc 107340
agcaggttcc cttctggccc agggtgtgtc tagaaatgct gcccaggagc cagggcctgg 107400
gatcgggagc tttaggaatc tgctttattg tactggggct gagctggcac ccacttgcaa 107460
gataaagtcc tttttactct tctctcacct caagcaggtg ggtctcccca tggacaccac 107520
agctgtgaat gtgcggggtc atatctgaag ctggcacaat acgacatggc accttgtttt 107580
ttattcaagg cacaagggct ctttagtcag ctggtggtga atcctactag gactaggtat 107640
ttcccttcaa ggcaatgggt tcccttctgg tccagaatat gtctagaaat gtcatctggg 107700
agctatggcc tagaattgag gcttcagaac tatgcttggt gctttatttt actgtggctg 107760
aactagtatc cacattgcaa gacaaagtcc tccctactct tccctctcct cccagagctg 107820
tgagctgtgg tacctggagt tgggggaagg ctggcacaag cactcccttg gccaccctag 107880
ctggtgtctc agtgggtcac atgtacccca agtccactga ctatgagccc agcacagtac 107940
catgacttgt ccaggaattg cagtccttct ggtctagact gcctttcaag tttatttagg 108000
accccagagg actttaccca cggtggtggg gcttaccaaa attaagattc ttttggtttt 108060
ttttggcaga gtttcgctct tattgcccag gctggagtat agtgacgcaa tctcagctca 108120
ccacaacctc cgcctcccgg gttcaaataa ttctcctacc tcagcctcct gagtagctgg 108180
gattaccggc atgcgctacc acctctggct aatttttttg ttttttagta gagatgaggt 108240
ttctccatgt tggtcaggct ggtcttgaac tcccgacctc aggttatccg tccgcctcgg 108300
cctcccaaag tgctgggatt acagaccata gtgcccagcc cgaaattcag attctaatca 108360
ctgggatgga caattcccct ctgactaggg ctagtctaaa tactccctct gtgggtgctg 108420
gctgaattct gtcctatgct gctttccact gtgacagggc agcactgagt ttcaatgcaa 108480
aatcccacag tcatttctct ctctctcccc cgagcacaca gattctttct ccaccccaca 108540
ctgcattgtg ggggaatgtc aggggtgttg gaggggcagt tcaagactat cttccttatc 108600
ttttttggtg tctttttcct tgataggatg tcaaaactgg gtactgtgat cgcttaccta 108660
atttttggtt cttatgaagg tgctttcttg tgtggatagt tgttcaattt ggtgctcctt 108720
gttggggatg atcactggaa ggttctgttt ggccaccatg ctctgtctct tctcccctgc 108780
catctccttt ttttacttag gggtttagaa tgtctaactg accaatatgt acagtcaggt 108840
ctcattctga attcacctac ttaatgacct tccaagctga ctaggcccag cgcttagtcc 108900
agcctccatg acggtccctc cacatcctaa ttagcctccc tccagttcat ttcacacaaa 108960
gctgctgtgt tcacctttct gaactataaa tctgcccagt actctaccct acttaaaatt 109020
ccgtatagac tgcccatttg ccctgagaat taaaagccaa agtcctaaac gtagcttttt 109080
aaaacttttt tttttttttt tttaattttt agatggagtc ttgctctgtc acccaggctg 109140
gagtgcagtg gtgtgatctt ggctcactgc aacctccgcc tcctgggttc aagcaattct 109200
catatgtcag cctcccaagt agctgggatt tacacgtgtg ccatcacgcc tggctaattt 109260
ttttttttta tctttagtag agacggagtt tcaccatgtt ggccagtctg gtcttaaact 109320
cctgacctca agtgatccac ctgccttggc ttcccaaagt gctaggatga taggtgttag 109380
ccactgcacg cagccctgaa catagctttt aagttccttt attgtcatat tccttttgac 109440
gagtctatca ttttctgact cacttgtaca tgtgtgtctc acccttggtc cagccattgg 109500
tgcttttctt tacttcttta tttttgttat tttattttat tttattatta ttttttaaat 109560
gagacagggt atcactatgt tgcccaggct ggtcttgaac tcctgagctt aagcagtctg 109620
cttgtctcag cctcccaaag ggctggaatt acagtgatga gctactgtgc ccagctcatt 109680
ggtgctatct tttttttttt ttttgagacg gagtctcgct ctgtcaccca ggctggagtg 109740
cagtggcgtg atcttggctc actgcagctc cacttcccag gttcacacca ttctcctacc 109800
tcagcctccc gagtagcagg gactataggc gcctgccacc atgcctggct aatttttgta 109860
tttttagtag agatggggtt tcagcgtgtg agccaagatg gtctcgatct cctgacctcg 109920
tgatccgcct gccttggcct cccaaagtgc tgggattaca ggcgtgagcc accgtgcccg 109980
gcccccattg gtgctattgt tttatgtgat agagccagct tctccctttt ctttggattt 110040
ttaaacatac tcttcctttt acttagacta ttctccatcc caacaccttt cctaaacttc 110100
tttcacacct tagactagct gacactttac tgagaaacct ttctttttta taggttgctt 110160
tttctataga ctctcttagc atttactcat tttattgtga agtgtctgat cttatttaaa 110220
tgacaagtat aagaggatag aaactatttc atatttttct cacccagcag gcacaatttc 110280
tgacatgtgg taagcactca gtaaatattg aactttagag gctaggacat ttgagtgctt 110340
tggtgactgt ggttgtgcta tataggtact ctgttattgt tagtttatag taaaagcatt 110400
actcttaaag tatgaaaaaa gccttattca gaacatttca tgcgtatagt taatattacg 110460
tagcttgtgc tcatggcaaa aatgtattac taaagttatt taagatattt aagtataatt 110520
gtttccttta tttagttaca gccaagttct acttctgaat ctatggatca actactaaac 110580
aaaaatagag agggagaaaa atcaagagat ttgatcaaag acaaaattga accaagtgct 110640
aaggattctt tcattgaaaa tagcagcagc aactgtacca gtggcagcag caagccgaat 110700
agccccagca tttccccttc aatacttagt aacacggagc acaagagggg acctgaggtc 110760
acttcccaag gggttcagac ttccagccca gcatgtaaac aagagaaaga cgataaggaa 110820
gagaagaaag acgcagctga gtgagtaaac ctggaactta gaccatcctg ttactcaatt 110880
aacttttttt tttttaaagg catttaggtc cttccaactg tgaagaatcc atctggactt 110940
ttagactact ttatacattg cccttagttt acaaacagct agtccaaaca aatgacatct 111000
taagtaaatg aggttattgc accctgtgct actcttctgt tcttcccctt ttttgtaccc 111060
cagggctaga aaaacaaggc ataaattaag aaaagttttt ctgtaaatga acaggagttg 111120
aaaaattatc aattcagggg acctatcttt actggattcc actcattagt caccctcact 111180
gtgctgctag gttgaaaaac tgccactgtc aaggagagaa gcatgcggtg cttctacttg 111240
gaattcaaaa tatttttcat cagaaactgt gttttagtta atgtttagat ttgttaagat 111300
agacttaatt ctgcacattc agtatattaa ttaaatggac ttttaggggc taacctcaga 111360
acttaactac cattgactta ggtgtttggg taccaaacaa tccagttaaa gctgaagttt 111420
tggaatgcag cttattgata aattggggac tgcttattct tgatttgagg caattttttt 111480
ttacagccat gactttttcc aggtatgtca tgtaaaatat cttctcacat aagaattact 111540
gcatgctaga atattggtat gttgactggt agctcatacc tataatccca gcactctggg 111600
aggtccaagc aggtagatta cttgaggtta ggagttgaag accagcctgg ccaacatgtg 111660
aaaccctgtc tgtactaaaa atacaaaaat tagccaggca tggtggtagg tgcctgtatc 111720
ccagctactc gggaggctga ggcaggagaa ttgcttgaac ccagaaggtg gaggctgcag 111780
tgagccgaga tcatgccact gcactccagc ctgggtgaca gagcgagact ctgtctcaaa 111840
aataaataaa taaataaata aaaggatact gttatgttaa gaattgcttt taaggatatt 111900
tcataagtag ctactgtctt ttcagctcaa gtgtttgttg attggccagg cgtggtagct 111960
catacctgta atcccagcac tttgggaggc tgagtcaggc agatcactta aggtcagcgt 112020
ggccaaaatg gtgaaacccc atctttacta aaaataaata ttaaaaaaaa ttagctgggc 112080
gtggtggcag tctcctgtaa tcccagctaa tcaggaggct aaggcaagag aatggcttaa 112140
actcgggagg cagaggttgc agtgagccaa gattgcactg ctgcactcca acctgagcaa 112200
cagagtggga ctctgtgaag gaaaaaaaaa aagtattttt tgattgcctt tgagaggaac 112260
ggttgtatat tactcagatt tttaaaaaat tgttctttta tggctgtatt ctttaaggga 112320
ttaaggaatg ggcaatataa gtgtatatgt ttcaataaaa acgattagtg atcttctagt 112380
gagaacagtt taaatctata tttagcaatt ttttttaaat tgtcaggtat ggaagatttt 112440
agagcaacgt aaagtccatg tagatttcac tggcctttat atttttttta ggcaagttag 112500
gaaatcaaca ttgaatccca atgcaaagga gttcaaccca cgttccttct ctcaggtagg 112560
tttattactt tctttgaggt tatctagtcc caaaaaaaga aaaattatta gtaatagtcc 112620
ttcttccata cctgccatct gaattttgtt ttagtgtgct gaaccaacct tctttctttt 112680
ttttacatgg ccattaatga atacttttta aacattaaaa aaaggtcttt gttttgtcat 112740
caattagatg tgatcttggg caaatctttg aatttctctg acccagaatt tgacgatggt 112800
tggctagcta ggctgtcagg tttatagata cgtcctctgc acctgagggt tttgcatcac 112860
tggattcaac caaccatgga tcaaaaacat agttaggata atctatactg aacacatgca 112920
gacgtttcct tgtcattatt ccaaaacaat acagtaaagc atttaccttg ttttaggtat 112980
tataaataat ctagagatga tgtaaagtat ataggaggat atgcataggt tgtatgcgaa 113040
tactacatga ttttatgtaa gggacttgag cattccaaga ctttggtatc ttcacagggt 113100
actgtaacca atcccccaca gatactaaga gatgactgta ctattgttat tattcgactg 113160
agatcataag aagatatatt tatttttaat ttttaaaaac acttccatca gtttcttaaa 113220
aatagctgcc actgttttta atatttttta attgacaaag ttttaagttc ctactgaaac 113280
attttttctt ttattgaaat gtgaaaattt atgtgctgtg tttttgtttt caataaaagg 113340
gacatagtta aagcaagtaa aattagaaag actgggaaaa tccgtcttta aattgcaata 113400
atagttcatc tgttaccttg agataattga atttattgtt gtttttgtag ccaaagcctt 113460
ctactacccc aacttcacct cggcctcaag cacaacctag cccatctatg gtgggtcatc 113520
aacagccaac tccagtttat actcagcctg tttgttttgc accaaatatg atgtatccag 113580
tcccagtgag cccaggcgtg caagtaagtc atagaatttg atgttcactt agcctcccca 113640
attgtttgta tctgacacca agcactcttt aggttttcag tgacttgagg gtgtgatggt 113700
tatgcatatg catttgaaac agacaggcat gcagagattc agtgtgttgt taagtatgag 113760
gacctaaatc tgagaatgtt ttctgtgaaa aagatggttt agatttactg tagtttgggg 113820
tttgttcctt ttagctgtgg gtatgatcta attttttaat gactaatgga gaatcaggaa 113880
accttctcat gcctagctct ctagcaatat aaaactaaga gtgacagaat accttgttat 113940
tatcataggt gcctaatgtt aatttttttt ttaattctct caagccttta tacccaatac 114000
ctatgacgcc catgccagtg aatcaagcca agacatatag agcaggtaaa ggtgagaata 114060
atcctgcctg tgtttgcttg tagtttgcat gctgcatgaa ttgagtaact aagtttataa 114120
tgaataaata gttgtagttt agctctgact ttttgatgag gctatgcatt ggcttttgat 114180
gaacaacatt acatagatat tcacatggat tttatgaaga aaaacagggg agaaaaaatg 114240
cccatcagtt gtgattatat agtatcctct tcaaaaagag taattggagg cctggtgtga 114300
tggctcacac ctgtaatttt agcactttgg gaggccaagg caggaggatt gcttgagctc 114360
aggagcccaa gatcagcctg gacaacagag actttgtctc tactaaaatt caaaaaaatt 114420
agctgggcat ggtggcatat gcctgtagcc ccagctgttt gggggactga ggcgagagga 114480
tcacttgagc ccaggaagta gaggctgcag tgagctgtga ttatgccact gccctccagc 114540
ctgggcgaca gagtgagacc ccgtctcaaa cataaatact ggctgggcat ggtggcttat 114600
gcctgtaatc ccagcacttt gggaggccga ggtgggtgta tcacctgagg tcagtagttt 114660
gagaccagcc tggccaacat ggcgaaaccc catctctact aaaatacaaa aattagccgg 114720
acatggtggc acctgccgcc tgtaatccca gctactaggt ggggctgagg caggagaatt 114780
gcttgaaccc gggaggcagg ggttgcagtg agccaagatc gtgccactgc acttcagcct 114840
gggcaacaga gtgagactcc atctcaaaac aaacaaacaa acaaaaaaca aacaaacaaa 114900
aaaaccagac taattggctg gacacagtgg ctccatgcct gatatcccag ctggaggatg 114960
acttgaaccc atgagttcga gagcagcatg ggcaatatag tgagacccta tctcaaaaaa 115020
aaaaaaaaaa gttaattcca aagctttttg atctgaaatc tgatttaaat ctgaacttaa 115080
atttgaagaa gagggtttgc tagattaatt tactagattg ctaaccttgc tttatatata 115140
cctacagtta tttccccaaa gccagaattt cttttgaagc agaggggcaa ctaacttcaa 115200
ccaatgttaa gatcctatta gaaggatgtt tcggctaggc ttggtggctc acgtgtaatt 115260
ccagcacttt gagaggctga ggtgggcaga tcacatgacc gggagtttta agaccagcct 115320
gggcaacatg gcaaaaacct atctctgcaa aaaaaaaata gaaatcttag ccagccgtca 115380
tggtgtgctc ctgtagtcct agctacttgg gagactgagg tgggaggatc aattgaaacc 115440
agaaggtcca ggctgcaggg aactgtgact gcaccactgg gctccagctt gggtgaaaga 115500
gcgaaaccct gcctcaaaaa gaaaaataag atggatgttt ctgcattaaa attagggagt 115560
tgtcgtataa tgtagttgca taaactagta ttctgtgctt gtgtggttaa agagccttcg 115620
tagaaaaaat cccacatttt tcttaaaagg aaatcttttg gccaggtgtg gtggctcaca 115680
tctgtaagcc caacactctg ggaagccgag gtgggcagat cacttgaggt caggagtaca 115740
aaaccatcct ggccaacatg gtgaaaaccc gtctctacta aaaatacaaa gatcagctgg 115800
gcatggtggt gcgtgcctgg gtgacagagc gagactccgt ccaaaaaaaa aaaaaaaaaa 115860
aaagagttct tttaatgttg gaaaatgcta aagggttttt tttttgccaa ccagttaatt 115920
tagagtgatt aactgctatc agttgagaaa ctatagaaag tagaataatt tatacagaaa 115980
agacatttct cagtgcccaa taattgcctt tctgacataa agttttcatt tttcctgaat 116040
taataagatt tcctcaatgt gtttttttgg gtgttttgtg tgtgtgtgtg tgtgtgtgtg 116100
tgtgtgtgtg tgtgtgtgtg tatgtgtttg atacagggtc ttgctttgct gctgaggctg 116160
gaacgcagtg gcgctatcat ggctcaatgc agccttgacc tcctgggctc aagcgatcct 116220
cccttctcag tcccctggat agcgggggct acaggtgcac accaccacac ctagctaatt 116280
tttgtatttt ttgtagagat gggttttgcc atgttgccta ggctggtctc aaactcctgg 116340
gctcaagcga tctgcctggc tctgcttccc aaagtgcctg cgcccagcca attttctcca 116400
tgtttgacct aattgtgatt tcatagatgt taactaaaac tcttaatttt cgttttctca 116460
gtatgctatt tttttttttt ttagccttgg aacatatgaa cctgttgaaa gaactctgcc 116520
tgaaataatg taatcaaatt atagagttta atcttatttt gagggccttt agaaattctg 116580
agaagaaagt gggttttttt ttttactgcc attttaatgt agtgttaagg tgttcatgta 116640
tcaccagcag gtgtagctgt tttcaatgat tacttaaaac aatgcaatgg gaactttttg 116700
ttgtcattaa aatataaaag gttactgtag taagagcaag catgacagtt tggctatctg 116760
atgggagagt cacattctaa cttcaggagg tactgtcttt ttaatagaaa tgatatactc 116820
agagtctggg cacggtggct cacgcctgta atccagcact ttgggaggcc gaggtgggca 116880
gatcacgagg tcaggagatc aagaccatcc tggctaatac agtgaaaccg tgtctctact 116940
aaaaatacaa acaattagct gagcgtggtg gcaggtgcct atagtcccag ctactcggga 117000
ggctgaggca ggagaatggc atgaacctgg gaggcagagc tggcagtgag ctgagatggt 117060
gccactgcac tccagcctgg gtgacagagc gagactccgt ctcaaaaaaa aaaaaaaaaa 117120
aaaaatagta gagaaagggc tttgccatgt tggccgggct ggtcttgaac tcctggcctc 117180
aagtgatcca cctccctcgg cctcccaaag tgctgggatt acaggtgtga gccactgctc 117240
ctggcctgaa tataccactt ttacctatca tcagttgatg aacatttgga ttatttcctt 117300
tttctggcaa tgagtaatgc ttttgtggat tttcatgtac aaattttcat atgaggctgg 117360
gagcagtggc tcatgcctat aatcccagca gtctgggagg ctgaggtggg cagatgactt 117420
gaggtcagga gtttgagacc agcctggcca acatggtgaa atcccatctc tactaaaaat 117480
acaaaaatta cactggcatg gtagcgtgca cctataatcc cagctattca ggaggctgag 117540
gcaggagcat cagaatcgct tgaacctggg aggcggaggc tgcagtgagc tgagatcaca 117600
ccactgcacc ccagcctgag tgaaagagtg agtctcaaaa aataaaaaat aaaatttttt 117660
ttcatgtggc cttagatttt catttctcct aaagtagaaa tgctgtgatg gaactgccaa 117720
acttttccaa agcagctgca tcattttgta tttctaccag taatgtacaa gtgttccagt 117780
ttctccacat cctcataaat aaccgatatg tctttggttt gggttatgtc cattctagtg 117840
gttatgaagt gtcattgtgg ttttttgttt ttttgtattg ttttgagatc gtgcccaggc 117900
tggagcacag tggcacaatc tcggctcact gcagccttcg cttcctgggt tcaagcaatt 117960
ctcctgcctc accctcccag atagctgggg ctgcaggcat acgccaccac accaggctaa 118020
tttttatatt ttttgtagag atggagcttc tccgtgcttc ccaggctggt ctcgaattcc 118080
tgagctcaag cgatccccct gcgtcagcct ccagagtagc tggggttata ggcgtgcacc 118140
accgcgctcg gcccattttt gtatttttag tagagatgga atttcaccat gttggccagg 118200
ctggtcttga actcctgacc tcaaatgatc cgcctgcctc accttcccaa agtgctgaga 118260
ttttagacgc gaaccaccat gccctgacta taggttatct ttttacttgc ttgatggtgt 118320
tctttgtaac acagttttta attttgatga agttcaattt atctgtttgt tttttctttt 118380
gttgctgttg ctcctgatgt catatcagac aaagcattgc ctaactcaag gccacagaga 118440
tttactccta tgaaacgcct ataaaactcc tatgattttt atagtttagc tcttaacatt 118500
taagtctaca atctcttttg agttaatttt tgtgtatgag atgagagtag tggtccaggt 118560
ttttcctttt gcttgtggat atccgttgtc cccacctcat ttgttgaaaa gactattctt 118620
tcctcttaaa ttgtttgttt gtttatttat ttttgagatg gagtgtcgct ctgatggagt 118680
ggcgctaact tagcttcact gcaacctccg cctctcagat tcaagcgatt cccctgcctc 118740
agcctcctga gtagctggaa ttacaggggt gcgccaccac acccagctaa tttttgtatt 118800
tttagtagag acggggtttt accgtgttgg tcaggctggt ctcgaactcc tgatctcgtg 118860
atctgcctgt ctcctggcac cctgggaggc tgagaggctg aggtgggagg atcacttgag 118920
ctcaggagtt tgagaccagc ctgtaccatt atgcctggct aattttagaa tttatcttaa 118980
agtataaaat gtgaatccaa tttatcttgt tctaaatgac tatccaaaat gttttaacca 119040
gttttattag tctgtaattt acatacaaga aaatgctcat ctttttatgt ttacatttta 119100
atgagttttg acaaatatat ttgctcatgt aactacttgc ttcatcagtg aagatggaaa 119160
acattgtgcc tgttcctctt ctctgtccaa ctgtacttta ttaccactag ctccagttaa 119220
ccagtaatct gccttctttt actatagatt agatttatcc tctttagatt tctttttctt 119280
tttttttttt tgattaggtt tttttttttc tttttttacg taaaaaaatc tttttttgga 119340
gacgtctcat tatattgccc aggttggtct cgaactcttg agctcacctc agcctcccag 119400
agtgctagga ttacagatgt gagccacctc agccagcccc tagatttttt tttttttttt 119460
aataaatgga atcaaacagc gtgtaacaga ggtgttcaat cttttggctt ccctgggtca 119520
tattggaaga agaattgtgt tgggccacac ataaaataca gtaacactaa tgatagctga 119580
tgaacaaaac aaaaaaaaat agcaaaactt ataatgtttt aagaaagttt atgaatttgt 119640
gttgggccac attcaaagcc gtcccaggac gcaagttgga caagcttggt atataatttc 119700
atatgtgtgt cctaaacagt gtagtaattt gaatttcatg ttagtatcag cttattcctt 119760
tttgtttgtt tgtttgtttt tgagatggag tcttgttctg tgtcccagaa ttggtctgca 119820
attccactgc ctcagcctcc caagtagctg ggattacagg cacgtgccac cacacctggc 119880
taatttttgt ctctctctct tttttttttt tttttttttt tttttagcag agacgggatt 119940
tcaccatgtt ggccaggctg gtctcaaact cctgacccca aatgatccac ctgccttggc 120000
ctcccaaagt gctgggatta caggtgtgag tcaccgtgcc cagccagctt attccttttt 120060
attgctgggt agcatttcat tttatgatta taccacagtt aatttaccca ttactagtcg 120120
atgggcattt gagttattgc cagcttttgg ctattatgaa tgaagctgct gtgagcattt 120180
gtgtacaagt gtttgtgttt ttatttcttt tagttaaata cctagaattg gaattgctga 120240
ggtatggtaa gtgcatattt cattttttta aaaaatttat tttatttttt atttatttat 120300
tttttttgag atgaagtctc actctgttgc ccaggctgga gttcagtggc gtgatttcag 120360
ctcatggcaa cctccctgtc ccgggttcaa gcaattctcc cgcctcagcc tcccaagtag 120420
ctgggattac aggcgcgcac caccatgcct ggctaatttt tttgtatttt tagtagagac 120480
ggggtttcac cacgttggcc aggctggtct cgaactcctg accacaagtg atccacccgc 120540
cccagcctcc caaagtgttg ggattacaga tgtgagccac cacacactgc ctggtaaata 120600
catatttcaa ttaataagaa actagcaatc ttctaaagtg attgtgtcat tttacattcc 120660
aactgatcag gtacatgtgt aggttccatg tgttctgcat ccttgccaac acttggtatt 120720
gtgttatctt tttaatttca acaggtctaa tgggtgtctt atggtatctc attgtgatct 120780
taaatgtaca tttctctgat gatgactgat ccaggagcac ctcatcatgt gtgtgtttgt 120840
tttcagctgt caaccttttt ttagtaaatg gttcaaatct tttttccatt ttatttattt 120900
atttatttat ttgatggaat ctcactctat tgcccaggct ggaacgcagt ggtgccatct 120960
tggctcactg caacctccgc ctcccaggtt caagcaattc ttacgcctta gcctcccaag 121020
tagctgggat tacaggcatg cgccaccatg cctggctaat tttgtatttt tagtgtaggt 121080
ggggtttcac catgttggtc atgctggtct ctaactcctg acctcaggtg atctacctgc 121140
ctcggcctcc caaagtgctg agattacagg tgtgagccac tgcgcctgtc ctaataattt 121200
ctttttgtct caatgtttct gcctgggtgc actggctcac gcctgtaatt ccagcacttt 121260
gggaggccaa cctggatgga tcatttgagc caacagtttg agaccagcct gaggaacatg 121320
acaaaaccct gtctttgcaa aaaaaaaaaa gaaaaaagaa aaattagcca ggcacagaag 121380
cgcattccta tggtcccagc tacttggggg gctgaggtgg gacaatcgct tgagcgaggt 121440
tgcgggggtt tggagggcga tggaggggtg atcgaggttg cagtgagctg agattgcact 121500
actgcactcc agcctgggca atagagccag accctgtctc acaaaaaaaa gaaaaaaaag 121560
tcatgtttct tttcttactg tgaaaataaa gttactactt ttagtaaatt attttaagtt 121620
atttatatat tctggttaca agtcctttct cagaatattg tgaatatttt ctcccagtct 121680
gcggtttttt ttgaagagcc agtattgtta attttaatga agccttattt atcaagcttt 121740
tctcttaagg ttcatgcttt tttgtatcat aataagaaat cttttacgta ccctaggtta 121800
tgaatgtttt tatggttagg tatatggttg atttcaggtt aggttttgtg tagggtgtga 121860
tgtaaaggtc tagcttcatt ttctccacca taaatattta ctcggtttct ctggcaccag 121920
cctctgtttt ccattggtgg ctttattttt tttctgttct tgaaacaaga gtctcgatct 121980
tgttacccag gctggagtgc agtagtgtga ccttggctca ctgcaacctc cacttcccag 122040
ggtcaagcga ttctgcctca gcctctcgag tagctaggat tacaggtgcc cgccactaca 122100
cccagctaat ttgtattttt tttttttttt tttttagtag agacagggtc tcaccatgtt 122160
ggccaggcta gtctcgaact cctgacctca ggtgatctgc tcatctcagc ctcccaaagt 122220
tctgggatta caggcatgag ccactgcgcc cagccatagt agctttattg aattcagttg 122280
actgtattgt atgtgtgtct atttgtgaac tgttttgttg tattgatctt tgtatatatc 122340
cttatgccaa ttctctcttt attgctgtta ctttgtaacc aacctttaag ttcatatgag 122400
tctcccagtt ttattctcgt caaaattact cttattctgc gttctttgaa tttgcaaata 122460
aattttagaa tcagcttggg attgtgcact gaatctttat atcagttctg ggagaaatat 122520
cttaacaata tggaatcttc attgaggtca tcatatactg ctccatttat ttaagtctta 122580
agtttcacca gtgttttcta gttttctttg tatcagtttt gtgcctgctt tcttaaattt 122640
atcccttaat atttcatctg ttttgtgctg ttgtgagtta tattttaaaa actttcaacg 122700
tttgtttatt cgtaaataga gatgcacttg atttttgaat attgaccttg tgtcttgatg 122760
tgttggtaaa cccactgttt ctggcagccc tttaagactt aaacatacaa tcatgatcta 122820
atcaccatgt tggtgttttt gggttttttt tttttgtctt attgtactgg tgcattactg 122880
aaaaaggcat gagattttgc catgctccca tttttagggg tgagacattg tctttcacta 122940
ttaagcatac agttaggtgt tacttcagtt cctaatttgc agaggtgggt ttgttttctt 123000
tttaatcatg aatggttgtt ggattatgtt caaatactta tcatctacta agtatatcat 123060
attgaccagg aacagtggct catacctgta acctcagagc tttgggaggc caaggcagga 123120
ggatcgcttg aggccaggag ttcaagacca acctgggtga tgtaggaaaa ccccatatct 123180
acaaaacaat ttaaaaattt gctgggtgtg gtggcacaca cctgtagtcc taactacttg 123240
agaggctgag gaaggagaat tgcttgagcc cagtagttta aagcagcagt gagctgtgat 123300
tgtaccactg tactccagcc tgggtgacag aaggagaccc tgtatttaaa gtgtgtgtgt 123360
atgcgtgcgc atagatggat agataataat gtaattccat tatggtcata caaactgata 123420
tgaaatgcca ttttatcata taacaagtgt ctttttgtgg ttgaatttgt ttctggattt 123480
ttcactctgc ttcactaatc taataggact accttctcat ccactcactg ccaacattga 123540
tttttttttt cagattacct tgaattttct gtttattttt ccatatgaac tctataatta 123600
acttactact aaaaaaatca gttgcctttt taaaaccaac tgatctttaa aatatatctt 123660
ggctgggccc ggtggcaggc acctgtaatt ctagctactt gggagactga ggcagaagaa 123720
ttgcttgaac ccaggaggcg gaagttgtag ttgagttgag attgcgcacc tgtactccag 123780
cctgggtgac agagcaagat tccctcttaa aaaaaaaaaa aaaaaaaaga aacagaaaag 123840
ataaatcttt ttacaataat ttgttccaat tagggtccaa gtcaggcttg caatttggat 123900
ttgtttatat gttgaagtct tttttttttt ttaattgttt catattgtgg taactttttt 123960
tttttttttt tgagatggaa tcttggctct gtcacctagg ctggagtaca gtggcacaat 124020
ctcaactcac tgcaacctcc ccctctgggg ttcaagcaat tctcctgcct cagcctccca 124080
agtagcccag cctttttttt ttgagacaga gtctcgctct gttgcccagg ctggagtgca 124140
gtgatgcgat ctcggctcac tgcaagctcc gcctcttggg ttcatgccat tctcctgcct 124200
cagcctcctg agtagctggg actacattcg cccgccacca cacccggcta atttttttgt 124260
atttttagta gagacagggt ttcaccgtgt tagccaggat ggtatcgatc tcctgacctc 124320
gtgatccgcc cgcctcggcc tcccaaagtg ctgggattac aggtgtgagc cactgcgccc 124380
ggccttgtat ttttaataga gatggggttt caccatgttg gccagcccgg tcttgaactc 124440
ctgacctcaa atgatccacc cgcctcggcc tcccaaagtg ctgggattac aggtgtgagc 124500
catcgctctc agccttgcgg taacttttta ttacgaatgt attgagacat taataaccta 124560
ggccagtcat gtttcatccc tacccattgt ctcttaaaag ctttgagtcc actggattat 124620
tctgaagcaa attctagaca ttgcatcagt ttatccacca acattttagt gtgtatcttt 124680
aagttggttt tggttttgtt ttttgttttt gagatggggt ctggctttgt tgcccaggct 124740
tggagtgcag tagtgcaatc atagctcact gctgctgcga attcctggtc tcaaaggatc 124800
ctccctcctc agcctctcaa gtaactgtga ctacaggcac atgccacctt gccagctttt 124860
cttttcttgt cttgtctttc ttcttctttg tttttttgtt tgttttttgt ttttttttga 124920
gacagagtct caccatcttt ctatcttgcc caggctagtc ctaaattcca gggcttaagt 124980
tatctttcta cctcagcctc ctaaagtgct aggattacag gccagcactt taggaggtgc 125040
tggatgagcc atcacaccca gccaagtcat aggttttttt gtttgtttgt tttttgagac 125100
agtgtctaac tctgtcaccc aagctggagt gcagtggcat gatttcagct cagtgcagtc 125160
tctaccaatt gggcttaggt ggtcctccca cctcaacctc ccaagtagct gggactaaag 125220
gtgcgcgcca ccatacctgg ctaatttttg tattttttgt agagacaggg tttcgaattc 125280
ctgagctcaa gcagtctgcc tgccttgact cccaaggtgc caggattaca ggcatgagcc 125340
actgcactca gccctcacag ttttaattac agtttttccc ttagtttttg tcttgttcat 125400
atccagcttg tcttgtattt ttttcccacg atctgaattt tgctgactgt atccctgtgt 125460
tgatatttaa agtagacttc tgtcccctgt aatctttgta aactgatagt aaataatgaa 125520
ggcttgatca gattgggttt tttttttttt tccccaatgt ttcacagatg tgtgtacttt 125580
cagtgaggag tcatgtaatc agtctttttc ctgataggag tagtcagtga gttcctagat 125640
gttttatcta tccaggagat aatatgtccc tttagcgcct taattttttt ggtgtgtttt 125700
ttagcagcca ttgatgataa ttgtctagcc caagatcagt tatttcctta ggggttgtaa 125760
aatggtgaca ttcttttcct ttcatccctt cttcaattat tgcctggaat atttctataa 125820
agaaaaactt tcccatatcc agctgtttgg ttaccctgag gtatagcttt cttaggaaaa 125880
gtaatttaaa atgttaatca tttccctttt taaggcagtc ttcaaaataa tgagttggtt 125940
ttctgttatc ctccaaaggt aaccagtgag gtggtttttt tgtcgttggt tcttactatc 126000
agtataaact tctggaattt tttttttttt tttaattttt tggagacaag gtctggctct 126060
gttacctagg ctggagtgca gtgggatgat ctgggcatac tgcagcctca acttcccgag 126120
ctaaggcaat ccccccacct cagcctccca agtagctggg actacaggca agcaccaccg 126180
tgcctggctt aatttttgta tattttgcag agacagggtt tcaccatgtt gcccaggctg 126240
gtgtcgaact cctgagctca agcagtctgc ctgtgtcagc ctcacaaagt ggtgggacta 126300
caggcatgag ccaccatggc aggccagaat cacaataaac ttataaatta acttgagaag 126360
aaatgattga tgtcttcatg atgttgagtc ttcctgttca agaacaaagt ataccttcaa 126420
tagcatatta aagtttatcc ttggctggat gcagtggctg acgcctgtaa tcccacctct 126480
ttgggaggca gaggtgggca gatcacctga ggtctggagt tcgagaccag cctggccaac 126540
atggtgaaac cccgtctcta ctaaaaatat tttaaaaaaa gtattagctg ggtgtggtgt 126600
gcacctgtag tcccagctac tctggaggct gaggtaggag aatcgcttga acccaggagg 126660
cagagagtgc agtgagtcaa gattgcacca ctgcactcca gcttgggcaa ccgagcgaca 126720
ctctgtctca aagaaaataa ataaataaaa ataaagttta tctttaaggt tttgtacatt 126780
tttttcagtg tatgccttag gtaggttctt ttttaatgtt agtgtaaccc agggacttct 126840
cttccattgc atcttctaag taattactta tgaagtacca tatatgaagg ctattgctgt 126900
ttatatgtta gtttttaccc tgctccttta ctaaattcca atcctttgag gtattggata 126960
aaaatatttt tagcattttt caaataacag gcagagtcaa gggcttggtt tcttttcttc 127020
ccctcctgtc ccctaccctc cccttttttg agacagggtc tcacttcttc gccgaggctg 127080
gagtgcagtg gtgcagttac ggcttaccgc ggcatctgcc tccctggctg aaaagttcct 127140
cccacctcag cctcctgagt agctgggacc atagatgcac agcaccgcag ctggctaata 127200
tttttgtatt ttttgtggag gcagtgtctc cccatgttgc ccagggtggt cccaaactca 127260
tgagctcaag cagtccgctc gccctggcct cctaaagtgt agggattata agcgtgagcc 127320
actgcgcctg gcctggggat catgttttaa catgagaatt agtggagaca aacacatgat 127380
atctaaataa tagcaccata gtatacttga ctagcttttt aattattttt taaatataca 127440
ggaaggtaat aagtaacaaa gtaataatag tgaatagttt aagctcagtt agcataatcg 127500
ggcaaacttt catttgataa aagtgataag tagttttcag tggctttttt gtttaccaga 127560
aggaggtggt ttttaaatac gtgcatccaa gataaaatat aaaaaaatgt tcaggtttgc 127620
tttcctacat agataaaata atatgtaact agctctccca aatttcagca acagttagtg 127680
aatgtttagc cacaaatttg cagttaatta tataatcagt tcttaggatt ttatgaacaa 127740
gttctatatt ctttgtgcct tatacctagt tgtaagcagt cattccacaa ttattttcct 127800
gaagtggctt ggttaatgcc acaccagaaa caggtcacag acaatagtgc tgtaagaaat 127860
gtgtgaggaa agaggcacat gggaagtagc tagctcgtgc tggaggaact ggaaaaaaac 127920
ctcacatggg agatgacagt tgagctgaat tcttaactag agttgtaaca gggcgaggcc 127980
cttacatgca gaccacctgt gtggattaag ataagacata aagtaatctt ttaaaagaac 128040
tattatttag aaacctggta tatgctacat ggtgctgtgt tatactgggt ttgagaaaga 128100
atgggaagtg ttacaaggat tcagtggttg gaaattaagg aagatagaaa gttagtgttg 128160
gatctgtttt ggctctttgg tcatgccttt gtttttctca aaatgaatgc agtgcccgtc 128220
ccagaaaata ccatatgaga agcgatttca taatgctgtg agagtctgtt acagggactt 128280
gatcaagtct gagggccatg agagaaagtc cctctgagga agttgctttc aagctgacac 128340
ctgaaggatg aagcagaatt atcccagctg ggatttggga actggtgttt gaggctgagg 128400
actagcatgc atgataggaa aataacccag agtggcagaa gtgggagtgg tatgagatgg 128460
catcagagac gcagattcag ggtcaaatca ttcagagcct cctagaccat gtgaacacat 128520
gtattatgct gtggagatac tgtttaatag gcagtctgct tttttttctg cagtaccaaa 128580
tatgccccaa cagcggcaag accagcatca tcagagtgcc atgatgcacc cagcgtcagc 128640
agcgggccca ccgattgcag ccaccccacc agcttactcc acgcaatatg ttgcctacag 128700
tcctcagcag ttcccaaatc agccccttgt tcagcatgtg ccacattatc agtctcaggt 128760
aaggctggta aggcctaact cttaattttt gtaccatata aaaaaacttt taatatggta 128820
aagggatttt cctttataat ttttgctttt gtgtgatggt agggtagata gctaaggact 128880
tggggaccct tttcaatata tattcgaagg ttactgatga ttgtaagagg ttcagaggaa 128940
acagccaaga aagatttgag agtttacagc tgtttctgga aatctggaaa ccatggagtt 129000
aaaaatctta actaaagtct gcttggctct atttgcagtg ttaatgtgct ttctttattt 129060
tttgtttgaa cacagcatcc tcatgtctat agtcctgtaa tacagggtaa tgctagaatg 129120
atggcaccac caacacacgc ccagcctggt ttagtatctt cttcagcaac tcagtacggg 129180
gctcatgagc agacgcatgc gatgtatggt aggaagcact ttgtttgtct cttccagtgt 129240
gtgtgactct tcttaattta agtttctgaa aacatactct atctaagaat aacctgacct 129300
tttatgacat tgagggtcaa gaatctgaag gaaaagatga acccatttct ttgcctgact 129360
tgctttataa cttttggcaa atagtttcta cttctgtacc tggtcttcag atctctttcc 129420
tgctttaact aaaatgtaat gatgtatata atggcaaagc atctttgtgg agaaaggtac 129480
ctttctcctc ttcctcatca atattatgct ttggtatatc ctgcctacga catgcaagag 129540
aattttataa taataaaagc ataaaggtgt tctccagcat gaaaacattt tgcttcacta 129600
cttgatctga gggtcactgg cattacatat tttttttgct gtttgttata atgataatac 129660
tatgtttcta catcatgctg tattttaatg gttgaatatt atgtcatatt agatatattt 129720
tagacatgag tcacacttta aatataacca atgtgaacag aatgctgaaa tgaaaatgag 129780
aagtatttta tgtaaaacta agcagtattt atatgtgaga ataataagca aaaaaaccca 129840
tcttcgtttt gtgactaaac agagaaattt gtgtagatca acttagcagc tgtctaaagt 129900
accaaaataa tagatttttc actgttgata atttaaaata aaatgtccat ttgtatatct 129960
tatgatacag aattaatgga ttgcttcaaa tgtttttcag aatatgtttt taaatagtac 130020
tgatttcatt aagatgtttt gttctgaata tttctgagaa ctaccgtagt gtcgtttagt 130080
tttcctattt gcgtttttgg ttgtttggag taggggataa ttttggttta ttcatacagt 130140
tgaaaagtgt actgctatga gaatgagatt atggttacat gtaactacat gggcatttca 130200
tttttaaagc ctctttgaac tttttgaaat actaagaata taaaattttt attttttaag 130260
tttagatgtc ctgaacgagt atgtttaggc aaaattgagt tatttaagaa tttataggct 130320
gggcgcagtg gctcacgcct gtaatcccag cactttggga ggccaaggct ggcggatcat 130380
gaggtcagga gatcgagacc agcctggcca acatggtgaa accccatctc tactaaaaat 130440
ccaaaaaatt ggccgggtgt ggtggcatgt gcctgtagtc ccggctactt cggaggctga 130500
ggcaacagaa ttgcttgaac ccgggaggca gaggttgcag tgagccgaga tcgcgccact 130560
acactctagc ctgagcgaca gagtgagact ccatctccaa aaaaaaaaaa aaaaaaaaag 130620
aatttacaga tttctggcaa accttcttct tgagacatta ctacttttca taccacctct 130680
gtcctttttg aagaataaaa gttttaacat tccgtaggtt aatgagaata ggacttgggc 130740
agcagcaatc atccttcctg tcacctgtaa cccacagctt atgctttctt cctggaggtt 130800
cttgtctgcc acaaaggctc actgctgata ggaatttgta tatgatcaaa ggtgtttagt 130860
tttataaaac agttaagtcc agtcttaatt ttccacatta tcactttcaa ttttgtattg 130920
tggattacgc attttaaata aaaaattgtg tgattgctac attttggaaa acattttttt 130980
caagaggccc atccgtaatt taattgtaaa agatactgac aaactaactt ggtttattat 131040
tttggttatg accccgtcat ttgacttgtc tttagttgtc ttaacgggga ctgaatatgc 131100
gtgcaaaggc acgattgatt tatcatgctg gcttttatgc aacttgtata tattttaaca 131160
attttcctgt ttgctaaagg cttaggttaa aagttcatta tgattgttta tacatttctg 131220
gtgaatacat catgatttaa caagtggaaa gaacatctct ttccttccat tttctggcat 131280
actccccttg gaatcagatc tgaaactttt aagctaaaat ttccattgca tttggagagt 131340
agttatttgt gtatgcatgc ttttgagaca ttgtagcaat aatactgtaa tgttgagccg 131400
aatctttctc ctcattgtgt tcattcactg ccaacatctg gcttcatctt ttggatgaat 131460
gttcattggt tttgaaacag cctatagggt aaatactgtg tttgaggtac agatgatttt 131520
cataactact tcctagaaca tgtccatttg aagagcagtg gggccttaga ccccaaagtc 131580
catttatgtg tgggcaaata ggaaatgttg caaacaaaac aaagcactag atctaatgtc 131640
cagtgaaatc tggaatgaac tagtcattag agccggttct ttcatgccag gaaaaagtta 131700
ctcagccaaa tctgaactac tctcctgcag tttacacagg tggtatttaa ttgctgtctg 131760
tatggaggca ggctaggagc aaggctgtgg acttgttgtg attgtcacta gttaatcaag 131820
attccctttg tggtgcttaa gaccctaaaa aggacactag gagctgggca tggtggctga 131880
cacctgtaat ccaagaactt ggggaggctg aagtggagga tcgcttagcc caggtgttca 131940
agaccagtct aggcaagatg gcgagatccc atctctacca aaaaaaaaaa aaaaaaaaaa 132000
aaaaaaaagc ccagtcatgg tggcacatgc ctgtagtccc acctacacag gaagctgaga 132060
tgggaggatc acttgagtcc aggactttga ggctacagtg agctatcatg gcaccactgt 132120
aatccagcct gggtgacaga gcaagaccct gtctctattt aaaaaaaaga aaacataaga 132180
aagaattgtt ttgttctatg ccatcataag ccataattta atctgcttaa gcatgttctt 132240
cattaaatct gcagtgattt atttgaatta ttagactttc aaagccttat tatatcaaat 132300
ataaacaaaa tttgaagtac attcttataa actacaacaa acttacatag aagtgttaat 132360
tttatactca tcttccctga acaatttata ttttataaat atattaaata tattgtcata 132420
aattttctca aaggaaccaa atactttgag tatgaattgt gcttttcttt ttaagctaca 132480
tcatatctag gtttttaaaa catttaatgc aaacagaaga acatgcaccc agatgttggt 132540
gacaatttta tgtcaccttt tctcattcat taattgttat agccatagcc aaaggcattg 132600
aaaacatagg accactaatg actgcaaaat gaaatcctga ttattgtttt taaattttta 132660
gtatgtttaa tacacatatg ctaacattac tgaacagtta aatgataaaa taggataatt 132720
attttattct aaaaaagtat tgaccttgac ctctttctag ctatcttaga aagggctttt 132780
gtcaaaaacc ttatctcttt gatgtctctt tttttgagat ggagtctctc cctgtcgccc 132840
aggctggagt gcagtggcgt gatctcagct cactgcacgc tccgcctcct gcgttcacgc 132900
cattctccta cctcagcctc ccgagtagct aggactacag gcgcccgcca ccatgcccgg 132960
ctaatttttt gtattttgtt tagtagagat ggggtttcac tgtgttagcc aggatggtct 133020
tgatctcctg acctcgtgat ccgcctgcct cagcctccca aagtgctggg attacaggcg 133080
tgagccactg tgcccagcct cttttttttt ttttattttt tatttatttt ttattttttt 133140
tttaattttt gagaaggagt ctccctctgc cacccaggct ggagtgcagt ggcgcgatct 133200
cagctccctg caaactccgc ctcctgggtt caagcagttc tcctgcctca gcctcctgag 133260
tagctgggac tacaggtgcc cgccaccaca cctggctaat ttttgtgttt ttagtagaga 133320
cagggtttca ccatgttggt caggctggtc ttgaattccc gacctcaggt gatccaccca 133380
cctcagcctc ccaaagtgct gggattacag gcgtgagcca ctgccccggc ctctttgatg 133440
tctcttaatc taacttccat cattgcctct accccatccc ttctaagaag ttactttaat 133500
tttttttcct ctcacatcta ctcttttttt tttttttttt ttttttttga ggtagtctca 133560
ctctgtcacc cattctgaag tgcagcggtg cgatctcagc tcactgcaac atctgcctcc 133620
caggttcaag cggtttttct gcctcagcct cccgagtagg tgggactaca ggtgtgcgcc 133680
accacgaccg gccaattttt gtatttttag tagagacggg gtttcaccgt cttggccagg 133740
ctgatctcga acttctgacc ttgtgatttg tctgcctagg cctcccaaag tgctgggatt 133800
acagatgtga gccaccacgc ccagcctcac atctactctt ctaatccatc taattttgtt 133860
ttatggtgat gcttttacct ttcagaaaca gtaataatac aacttttccg actaactaga 133920
gccattagga agaattagat ccagaatcct tttttgattt gtttttggta gtttaatgca 133980
gataagtaag aaaatatagt taagttaaaa aaaaaaaaaa tgaaaagcat ccataatccc 134040
tccacctgac aactgccttt taacattttg atgtgtatcc ttccaggtgt atttaaatac 134100
actcaaatac cctacccctt tatgtagaca tgttttaata agaaataata ttcatgttta 134160
tattcttgct atgatcctaa atttttggat ccattactag ataatctttc aggataatga 134220
catttccatt agtaatgttt ttgcaaaatt gtgtgtctat tgaattaaac ttgtaaaata 134280
gttttatttt ggtacatgat ttatatcaag gttgttcagt agaatgccat gttggtgttt 134340
ttattagata atgattttat tccttttact tttaagcaag tcagcatgac aacttgacac 134400
ctaagtacag aagaacagtg tcttccggtt tagtcctttc ttttaaaatt ctgtagcagt 134460
gtttaaagtg cttgtcatct cttatgaaaa tgaattatgc atgaatacaa aaagaaatta 134520
ctaatatgtc aacctttcca gaaaatttgg aaaatgcaca cctcaaaagg ctaatttacc 134580
tttctatttc ccaaattcag catgtcccaa attaccatac aacaaggaga caagcccttc 134640
tttctacttt gccagtgagt tgggtttttt atactaattt ttaattgtac agtaaaacac 134700
tttttaaagg atacatgtta agggagtaga cttgttgaac aatattttcc ttgtgccagt 134760
caaattattg aaagtactta tatatataaa taattcagtt tttaaaatgg aaatacccaa 134820
tttaagaagg ctggagttaa tgaaaaatgg agttgtttca gaaatcaatt tttgcatacc 134880
aagcaaatgt gactgggaaa tgcctaatat tttccttgtt agagaaactt cctaaacagc 134940
tttatacaca cacacacaca cacacacaca cacacacaca aacacacaca cccaagccac 135000
aagcttggta taaatttaaa atgtttattt atacacacac acacacacac acacacacac 135060
acacacaccc caagccacaa gcttggtata aacttaaaat gtttatttat attctgataa 135120
gatgaaattt atgcctacca ggatttttaa ttgaatagga ttgatgaaat actaagggaa 135180
aaacttttca gtcctgtgca tggctaaagg tttaaaatac tcaggaaggg ccaggcacgg 135240
tggctcacac ctgtaatccc agtgctttgg gaggctgagg cgggtggatc atctgaggtc 135300
agcagttcaa gaccagccta gccaacatgg taaaactcca tctctactaa aaaatacaaa 135360
aatcagccat gcatgctggc atgcgcctat aatctcagct actagggagg ctgagacagg 135420
agaattgctt gaacttggga ggcagaggtt gcagtgagcc gaagtcgtgc cactccactc 135480
cagcctgggt ggcagagcga aattctgtct caaaaaataa aatattcagg aagcagaccc 135540
ctcaggatat cttgagctta agcaagagat catgacctct caggtcatta tcttggacag 135600
cacaggtccc ctctccccac ctggcaaaaa gtacagaaat agttgctcct tcatggagaa 135660
agtctgggca gagctttctt ctggaaatga acttttaagg tacatttttc ctatttgtag 135720
ggcaatttgt aaaaataagg gccggacgtg gtggctcacg cctgtaatcc cagtactttg 135780
ggaggccgag gtgggtggat tgcttgaggc caggagttcg agaacagcct ggccaacatg 135840
gtgaaaccct atctctacca aagcatggtg gcacgcacct gtagtcccag ctacttggga 135900
ggcggaggca caagagttcc atgaaccctg gaggtggagg ttgcagtgag ctgagattgt 135960
accactgcac tcaggcctgg gcaacagaga gagactctgt ctcaaaataa aaaataaaaa 136020
taaggctagt cttggacttt ggtatttaaa taggaaggag tactaatatt tgtagaaatc 136080
ctttagaaat ttgtgccatt aatattgtca ccttgtatga aatgttgtgt tctagaggat 136140
attaaggatt caaattttat gttaggcaca ttttgagtta ttttggggtg actcaatgtc 136200
tgactctact aaatgccata ttagcattta aaatgcattt gaccttaaat ctttgttaat 136260
tatgccatga cttggtatcc aaaaataagc tgatacatac atacatacat atatgtgtgt 136320
gtgtgtgtgt gtgtgtgtat atatatatat atgtatgtgt gtatatataa tttatttggt 136380
gctaggaaat gttaaattta atcctttaat agatgctctt taaaaaggag tcttgctgta 136440
tgtatatact attaaagggg aaactatgtc tgtgattgta gtgtgtaaaa gatagtaggt 136500
gattttatta tgtactcaat ttgaggtctc aaatgtagtt atcctcacca tcttactgtc 136560
tctgttagta gtttggtgtt gttttcctgg taagtagcta aggtccttaa tcattaacac 136620
ctaagcctta attgccttag cacaacttcc cctaaaaggg agtatcagta ctttttaaaa 136680
gaaactaaca gttgggctgc taatttaatc tgctgcttca tttccccctg ttctaagcca 136740
ttttatgatg gtttggtcaa gttgcctttt attccccttt tagagttttc aactttcctt 136800
cacttccctt tttctgaatt taacatcaga tttacaagtt ggaagatttt gttttgtttt 136860
ataagttttg caatgctggt gatctcttat gacttgtgca tccaaagtca aaatgacaaa 136920
acctagttac aaattaaaca cacagctttc tgtacttaat ttgcttcagt gagatcacag 136980
ctgaggaaac tagttctgga atgtggttag tgttattaag gatttttgac tgatcatatg 137040
tttagaatct taaatattta tgtcaaggaa cactgagtgg gaaacttctg gactaggtct 137100
ggaccaaaga agcatatgtc tttgattatc tttaatctaa aagattttat gaagactaaa 137160
gttttataaa tagaagttta actgatgaat aaatcagtat tacaaataaa attaacttta 137220
tttttaacct ctctgggatc tttagccaga atgagcatat ataacaaaag cagtgaaata 137280
atatgtgtgg gtcagaaccc actgcccttc ccactccact ctccttttcc ctgattctcc 137340
tgtgtttttt ccttctttac cttatcttgg ttcctttttt tttttttttc ttttgagatg 137400
gagtctcact ctgtcgtcca ggctggagtg cagtggtgcg atctcggctc actgcaacct 137460
ccgcctccta ggttcaagca attctctgcc tcagcttcca gagtagctgg gattacaggc 137520
gcctgctgcc acacccagct aatttttttt gtatttttag tagagacagg gtttcaccat 137580
cttggccagg ctggtcttga actcctgacc tcgtgatcac ctacctcggc ccctggttcc 137640
ttttttgtct ctcttgtctt ccaagctatt tttttccttg gcttttaaat tttcttccta 137700
ccctgctttg tgtcactgtc acttaactgg cctatcaagg aaccgaactg tatttttgtt 137760
actagtattg atttaaagta taagtttcac atttctccca atttattatt attatttatt 137820
tatttatttg tttattttat tttttgagac ggagtttcgc tcttgttgcc caagctggag 137880
tgcaatggtg tgatgtcggt tcactgcaac ctccacctcc cgggttcaag ctattctcct 137940
tccccactct ccctagtagc tgtgattaca ggtgcctgcc accacgccca gctaattttt 138000
gtatttttag tagagacagg gtttcgccgt gttggccaag ctggtctcga actcctaacc 138060
tcaggtgatc cgcccgcctc ggcctcccaa aatgctggga ttacaagcgt gagccaccgt 138120
gcccggctcc atttctccca atttcaaatt caaggaggaa aagaattcct gattaaggta 138180
cttctttcag atcttttgag ctagaacaaa aaaacaaagg gaaatatttc taattaactc 138240
tttttaaatt ttgtttacaa cgtatgatac atattttaca catcctttgt ggtttttgtt 138300
cgtcttgttt ttaatcaatg ccttgcaagt ttaccggtat ttaggtaggg aaaggatttt 138360
gtttttgttt ttttaaacaa agcctatgta cattcactca gcttgggtat ttgtgctatg 138420
catgcaaatt agctatagat tagaaaaccg tattatagtc tttaaatact ggtaaactta 138480
aattgcagag atgcctttta aaaatgcata gtaaaaatat ttcatcttta cttttctctt 138540
caaatgattt taagattttt acatttttcc agttgatgaa taacttaaat tatgagattt 138600
catgggcata attattttct atatttattg ttacttttta atattcttaa tactttgctt 138660
agaaggtatt taaaagtgaa atttcaaact ttttagtaca aaatttcttg aataaataaa 138720
gttacaaaaa aaaaacaaaa acctctgaga ttccgtactg tatctttatg aacctccatg 138780
aacagaattt gggatttggg aattgctttt ccttagacag atttagattg ttacaaatga 138840
catttttaag aggctggggt ggcggtaggg gttagtgcta atggtttaac agtaggggac 138900
catggacaac tgtagacatc actatccagt agaacatttt gtggctgggc gcggtggctc 138960
acgcctgtag tcccagcact ttgggaggcc aagacaagtg gatcacctga ggtcaggagt 139020
tcaagaccag ccagaccaac atggtgaaac cctgtctcta ctaaaaatac aaaaaagtta 139080
gccaggcgcg cctgtagtcc tagctactca ggaggctgac acaggagaat cgcttgaacc 139140
cgggaggcag aggttgcggt gagctgatat cacgccactg cactccaccc tgggcaacag 139200
agcgagactc cgtctcaaaa caacaacaaa actgcactgt ccaccgtatt agctacttag 139260
ctacatgtgg cttttttatt attcaaaaat aaatttttag gccgggtgca gttgctcaca 139320
cctgtaatcc caacactttg ggaggccgag atggacggat cacttgaggc caggagtttg 139380
agaccagcct ggccaacatg gtgaaacccc gtctctacta aaaatacaaa aattagccag 139440
gtaatcccag ctactcagag gctgaagcag gagtatcact ttaacccagg aggcggaggc 139500
tgcagtgagc cgagatcgct ccactgcact ccagcctggg tgacagcaag actgggtctc 139560
aaaaataaac aaacatggcc gggcgcagtg gctcatgcct gtaatcccag cactttggga 139620
ggccgaggcg gatggatcac ttgaggccag tagttcgaga ccagcctggc caacatggtg 139680
aaacccgtct ctactaaaaa tacaaaaatc agccaggcat ggtgatgctt gcctatagtt 139740
ccagctactc ggcaggctga ggcaggagaa tcgcttgaac ccgggaggcg gaggttgcag 139800
tgagccgaga tggtgcccct gcactccagc ctgggcaaca gagcgagact ctgtcaaaaa 139860
ttaaacaaat aaatacattt ttaaaatgaa cgtaagattt ttacaagtac aacaaactca 139920
ggttcgaaat ttacatcaaa tcttttagac caagtcagtg cctatacaac ttggaggagc 139980
tggaagtaaa cttaatgagt atgatgatga tggagggcct gttaataagc caccaagtta 140040
gaaaaaaagg actgtcttat agacttatgg gactgtgaag ctcaggaagg cttcatcgtt 140100
tgtacatcat ttgttctagc tcccagaaga cgttcactac tcttaaaaac attcagagac 140160
tatgttgcca cagttttctt gttaaaatat tctggcatat gttaattcct acagtctgga 140220
aaattttccc agtgtataaa caaagctgct gtatccagtc taaactggat atgaaggaat 140280
attaatgcca gctgtggcat tggcagtgga tgcacaggtg atcctagaac tggctctttg 140340
ccttgccctt tcccctgcta agagatagct ttgcagctgg agacgtaact gttagggctg 140400
gagagttggt ggcccttagc cctacaacac ctaggattat agaactgctc catgtgccta 140460
gcctaaccct ctgcacacca tttacgtgga atatacccag agccgtctat gctggtgact 140520
cggcagcctt gcctaccaga ctgctggaac tagggtgcct cttcccaaag ctgtgcttgc 140580
ttctctcacc aatcagtcct gcatatgtct gtgtttgcta acacgttata tgaagaatgt 140640
ggggaactat tttggaatca tttctgtgta tgggcttatt atcttgaggg attttaggat 140700
ttgtttctca agagagggct gggaactata ccttgctaga gttgtcttga gaacgctcta 140760
ttctcagctc attgcctcgt ggaggttagt tttttatcat cggtgtgctg tccatagtca 140820
ctggaagcag tgaacacatc ctactctgct tctgattctc aacttactgt ttttgaagca 140880
catgaacagg ccaggcacgg tggctcacgt ctgtaatccc agcactttgg gaggctgaag 140940
tgggcggatc atttgaggtc aggagtttga gatcagcctg gccagcatgg cgaaacccca 141000
tctctactaa aaatacaaaa attagctggg cgtggtggca catgcctgta atctcagcta 141060
ctcgggaggc tgaggcagga gaattgcttg aacctgggag gcagaggttg cagtgagcct 141120
gggcaacaga gtgagtgaga cttatatctc aaaaaaaaac aaaaaacaaa aaactgaaag 141180
acatgaagaa atggtttttg taccaaggtt tggcccacgc tgagattcac aaagaactgg 141240
ctttcagttc ttatctttat tttgatttaa actggcccat catgttgtcc tttgaagtta 141300
gtctagtaaa tttctttcca aagggctggg gcactcagaa gggagtttac ttttctatat 141360
ttatttcata aagcaaagat gggagatcct ccattagggc ttgggaaagt aaactgagtg 141420
gcagaagggc tcctgtgatt agctgagaga gactgtggtc cttcggccct gatgatagat 141480
ccctggcctt gccacatacc atacacagtg cccgcacccc catcccccac cacacccaat 141540
atagtctgtg ccctcaggac attgctccag ggcagtagca tggtgaggtt agcctgatga 141600
tggccttgag ctaaagagtg tgcacctaaa atgcacttgt ttgagtagtt tctgcctatg 141660
ccttcaagtt gcctttttgg gaaaacctag tgaccgttaa gagtaaatgc aaactaattt 141720
gattttaata tcatatgtag agctgtatta tatgaaccaa atgctagtct gttaagcaat 141780
agctacactt attttttcaa gacaatggat ggtttaaatg gagtcatcta tagaaattgg 141840
tagtggcgtg agttatgcat tgtaaccatc aagaaagttc agttgatgaa gtgtagagga 141900
gcgatggagg ttgtcagaca tcggttgtgt acatgctcct ttttctttca ctttagtttc 141960
cacgggctcc cttgctcagc agtatgcgca ccctaacgct accctgcacc cacatactcc 142020
acaccctcag ccttcagcta cccccactgg acagcagcaa agccaacatg gtggaagtca 142080
tcctgcaccc agtcctgttc aggtaagggc aactcagagg tctgcatgga gtggcttctt 142140
tatcctagta tctgagtgct ttcttcaggt gccaggtatc gcatcgtcag aacacatggc 142200
atgtccaccc tcgtgaagat ggatacagct gtgcccctgg ggtggtggtt ttaagaatca 142260
catttaaagg ctgggcgcag tggctcacgc ctgtaatccc accactttgg gaggccgagg 142320
cgggtggatc acgaggtcag gagattgaga ccatcctggc gaacactgtg aaactccgtc 142380
tctaataaaa atacaaaaaa attagccggg cgtggtggtg ggcgcctgta gtcccagctt 142440
ctcgggaggc tgaggaagga gaatggcgtg aacccgggag gcggagcttg cagtgagcag 142500
agatcgcgcc actgcactcc agcttggaca acagcgagac tctgtctcaa aaaaataaaa 142560
aattaaaaaa aatcacattt aagatacatg ttgataataa ggtgattgga taagctctgg 142620
aaacttgcag taatgaaaaa tcaaatttaa cataaagttc ataaggcaaa ttcctatttg 142680
cttgggactt tttaatttct aaggtttatg tgatgaggtt attttcctat gagcttcttg 142740
aattatgttt gctaatggag gcagttaaag atgtctttga tatctatcag ttccctgggg 142800
cagtagtctt ttttgacttt agtatgtatg ctcagaagtt tctaactgcc agactgagaa 142860
tcaggcttct gtaccctaga aaggagttgt ccagatggga ggcacctcca gccttgctct 142920
taccaccctg tacattctcc tgtactttcc agtgaccctc atcataggcc caagtgtgca 142980
aagcttagct ttgtgggtat cccttggctg cttttcatta aagaagtttt cctctcaatt 143040
ctttcctgtc gctttgcagc accatcagca ccaggccgcc caggctctcc atctggccag 143100
tccacagcag cagtcagcca tttaccacgc ggggcttgcg ccaactccac cctccatgac 143160
acctgcctcc aacacgcagt cgccacagaa tagtttccca gcagcacaac agactgtctt 143220
tacgatccat ccttctcacg ttcagccggc gtataccaac ccaccccaca tggcccacgt 143280
acctcaggta ataccagctt tagccaactt tctgtgaagg ccaagtagaa tgtgaaggtt 143340
atcagtaagc agctagaggc tctcccagct aggaaaccct gtgtgtcatg ccatttgcct 143400
gtctcccttt ccctctcaaa tacacgtgat ctggccctaa gggaatgttt gtgtggtttt 143460
gtcatgggat cagtgaaggt gctgattggt cagtccttta gttttccaac tgagacctta 143520
aaaatatctt tgactctgga atgcaaccca gtccttcttt cctttctgtg tctgctttgc 143580
tatgtctata tagcctcact actatatata tgtgtacata tatattcccc tacacactta 143640
ccttggaagc caggcaggga tgatggcctt cacagagtct cagctctccg aagtgactac 143700
cggggcctgt caacttgatt gttactcaca tgagttccag acacatctct ccaattgttt 143760
tccctggtta tccatatatc tgctttgacc ataagttgta ctcttgagag ggcttggcct 143820
tggacattgg tgcagtgtaa ctagaagctg gaagcaccca ggtggtccca tttttcttta 143880
agagcagccc tggaagcact ttggagctca cctccagtgt aagctgctac aggtgaaagg 143940
tgtgcttgcc atctcagtgg ttgctgtctg catcagctgc tgacaaaggt ccctgcactc 144000
cagggcccag gggattgtct taatgaggag aaggagctgc actgaagttg ggctctaacg 144060
ctggccttga ggccctccct ggggctgtta cgggtgaatt ggctgtatta gatgtctctg 144120
ctactttcat aacagaactc tctgaggcgg gtctaagtga gacctgccac aatgaattcc 144180
atttcctgtt aaatagtgcg ccagtgaggc tctggcaagg tgtgggctag agatgcgact 144240
cagttggatc tatctctcag aaggctacct tgtaagtaga gttccacagc tctgggaagt 144300
ttgggcgtcc tcaccctgca aagtttaggt tctgtggtgt agcgcactgc agttgatttg 144360
ctttttgata gtggggaggg aagccggttt ggtccgtgtg ggccagcgtg gtttggtgga 144420
gtcagcttca taagagctgg ggtcctgtag gtgtctacca gaggctggtg gctaagtagg 144480
catgtgaact tacatgtaag tcagggatcc ctaaaacctc actctgtttt tgtgctgaaa 144540
gggcaaaaag gttaacacag ggaagctcaa atttgccatg tgcccgtttg aatatgtgag 144600
agtaaaaacg gcatttcatc caaggcttat cgtagtctag aacagtgcac agtgtgggaa 144660
aaaggaaaca agggctcttc ctggccctgc caaccccctg cagagctgga atccagctgt 144720
ttgggctgac taaaatcacc tttccaactt gacagtgagt gagaccaggt tgaacttggt 144780
acagagacgc tgggctggcc cagatgactt caggttactc ctttccatct cactggagcc 144840
attaaaaact ccaactcctc ctcctcctcc tgctccatca gcatatctct gagagagtca 144900
cgggggccta agagtctctt ttcactgcct ggtgagcaga ccagaagcag agggagagag 144960
gcaaatgaac agaggtccaa gtaattcaca tacttgactg tgacagtctc tgcttattaa 145020
tgtaatctgt tttcctattt gaaagggatg ttatctgcaa aactacctca ggccccacat 145080
ggcagcctga ttctgaagca tcattgaatc ttgtatgata ttaagttgag aaagctgccc 145140
ttggatccag tgtctaatct ttgtgaagat cttaccccat acatagaata caatgatcag 145200
aaatgtcaag ggttaggaca gcacagccct gacttctacc caggctcact tgttgcctgc 145260
tccctgaccc ttgcaggatc tgcccaaagg tgaagcgcgt cttcaggtca atagataatc 145320
tactagagat tgtccccaga gaacagaact gggccctgag gcccaccgtt gccctttcct 145380
gagagtccca gcccagtgaa aggaacacag ttgacatgtt gttgaagccg gagatgttgc 145440
ctgtatgcgt aaaagagctc tctgtttcag gctcatgtac agtcaggaat ggttccttct 145500
catccaactg cccatgcgcc aatgatgcta atgacgacac agccacccgg cggtccccag 145560
gccgccctcg ctcaaagtgc actacagccc attccagtct cgacaacagc gcatttcccc 145620
tatatgacgc acccttcagg tgaggcgtgt gtgtgcaggg gccgccgggg caccccaaag 145680
cattctgctc gcacaggtgg aatggcaggc agggccagtg cttcaagccc cgcatttgag 145740
aactagcaag acccgtccag gagtgtgcac aggagggact gtgacgatca gttcagcatc 145800
agggcctgag gcttccggga gccgagtctg tgtgtgttct gatggtatac aggatttggc 145860
ttgatgagaa gcagcagcag cagcaacagc agcctgatgc atgcctagga ctcagttggc 145920
cttccttgtt atgacaggct ggacagggca gtgttttcct tcctgagtcc caaaagtctg 145980
acatgtgggg ggttattacc atggcagagt ttgattgtag ctctggagaa gatactgctg 146040
agaaagcgct gtggatggac tggctttgag tgtagcgtta gccccagccc ctgaacaggg 146100
gagagcgccc tgtgattgtg ctctactact tgatggctgc catggcgata cttcacagtc 146160
tgacctgtta ttctgaaagc aatactggtg cttggctaat atttggggag ggggtttgtt 146220
aaggcctttt tttctacccc atgaacaagt cttctgggag ttttatctga agtggtttta 146280
cgtctgactg gtttgtttct acccacccac ccaaccctcc ccactttggt gcagatggga 146340
gggggaaaag cgaattcaat tttgagtttt gttcagctag cacgaggata gtttacaatc 146400
atgtgctgca gagacactag gctgatgtgt ggtgttgcca gttttctgtt tcaatgttcg 146460
cttttctttt tacagtacaa gcccaccacc aacagcagtt gtaaggctgc cctggaggaa 146520
ccgaaaggcc aaattccctc ctcccttcta ctgcttctac caactggaag cacagaaaac 146580
tagaatttca tttattttgt ttttaaaata tatatgttga tttcttgtaa catccaatag 146640
gaatgctaac agttcacttg cagtggaaga tacttggacc gagtagaggc atttaggaac 146700
ttgggggcta ttccataatt ccatatgctg tttcagagtc ccgcaggtac cccagctctg 146760
cttgccgaaa ctggaagtta tttatttttt aataaccctt gaaagtcatg aacacatcag 146820
ctagcaaaag aagtaacaag agtgattctt gctgctatta ctgctaaaaa aaaaaaaaaa 146880
aaaaaatcaa gacttggaac gcccttttac taaacttgac aaagtttcag taaattctta 146940
ccgtcaaact gacggattat tatttataaa tcaagtttga tgaggtgatc actgtctaca 147000
gtggttcaac ttttaagtta agggaaaaac ttttactttg tagataatat aaaataaaaa 147060
cttaaaaaaa atttaaaaaa taaaaaaagt tttaaaaact ga 147102
<210> 57
<211> 16310
<212> DNA
<213> Intelligent (Homo sapiens)
<400> 57
tccactgggt gacgccagct gggctcctga gtttagtggg gacctgcaga acctttatgt 60
ctagctaagg gattgtaaat gcaccaatcg gcaccctgtg tctagctcag ggtttgtgaa 120
tgcacgaatc gacactctgt atctagctac tctggtgggg aggtggagaa cctttgtgtc 180
tagctcaggg attgtaaaca caccaatcag cgccctgtca aaacagacca ctcggctcta 240
ccaatcagca ggatgtgggt ggggccagat aaaagaataa aagcaggctg cctgagccag 300
cagtggcaag ctgcttgggt ccccttccat actgtggaag ctttgtcttt ctttgcaata 360
aatcttgctg ctgctcactc tttgggtcca cactgccttt atgagctgta acactcacca 420
cgaaggtctg cagcttcact gctgaagcca atgagaccac gaaccccccg ggaggaatga 480
acaacttgag acgcgctgcc ttaagagctg taacactcac cgcgaaggtc tgcagcttca 540
ctcctgagcc agcgagacca caaacccacc agaaggaaga aactccgaac acatctgaac 600
atcagaagga acaaactccg gacacgccac ctttaagaac tgtaacactc accgcgaggg 660
tccacggctt cattcttgaa gtcagtgaga ccaagaaccc accaattccg gacacaccag 720
ctactaggga ggctgaggtg aggggatcac ctgaatccag gaagtcgagg gtgcagtgag 780
ccgagatcat gccgttacac tccagcctga gtgacagagt gagatcttgt gtcaaaaaaa 840
cagaacaaaa taaaacaaga acgttgaata ggctgtgtgt taattctgag atggagtcca 900
gacttaagaa tgatcctgag gcttagaccc atatccaaga ggatgattcc agcctggcac 960
ttataggttc ttcaggcact tcagatgcac cctgtcctga attaagccct ttgtccttga 1020
acctgctttc cttggtaaac agcaccaagg gggctagaaa cctgggggct gcccttacct 1080
tccctctctc accatgcacc tctaatgggt ggctggactt gtggttgcat ttccgtgatc 1140
tcccagcttt cttccagtga tggccttagg tgggctctta tcctgtctcc caaatggcct 1200
ctctgccttg agtctcaccc catctgctct cagtccaccc actgagctat tccagagacc 1260
attctgactc cctgtggaca cccctctggt ggcttctcct ctctgtcagt tagaaattgc 1320
ttttgactgc atgtaacaaa tgtggttacg ctatttaacc aaataaaggt ttatttttct 1380
cgtgatgaaa agtacacaga taagcagcct acttccatcg ataaccattg agggtttctt 1440
atgactctta cagcaatgaa atgtgtattt acagtataaa gatatacaat tttaaggttt 1500
taatataatt gggcctaagc acagtatttt ttgttttagt tttcaactgc ccaggtgatt 1560
ctattgtgca gccagggttg ataaacactg catctaggcc cagtgccttt gatttgcagc 1620
tgaggtctag agagaattat tgaaactgca gtcccagcta cttgggaggc tgaggttgga 1680
gaattgccta agcccagcgg ggtgaggctg tagtgagtca agactgcacc accgcactcc 1740
agcccgggcg acagagcaac actccatcta aaaaaaaaaa aatttctggt ctaccttttt 1800
gcccaccttt taaccacaga ggtccccaaa catgaatttt cactctcagg aaggctgaaa 1860
tgacacatta caagcggttt agtcatctgc acgtgccgcc atctgattta aggcatctat 1920
tcctcctcac cattcctgac aaagttgaac tgtctacatg tgccacattc tcctctttct 1980
ctaattcctt ccctccttcc ctcctccctt tcttccctcc ctccctcctt ccttcttctt 2040
tctctttctt tttctttctc tctttctctt tctttctctt tctctctcac tctcttttct 2100
tctttctgac agggtttgcc tgttctgctt ctttaaaccc tggggttcaa gtgcaaaggt 2160
ccctctcatc tgatttccct attttatttt atttaagtta gatactccac gatgatgatg 2220
atgattattg ttgagacagg atttcattct gttgcccagg ctggagtgca atggtgcgat 2280
cacaactcac tgcagcctca acctcctggg cccacgcgat cctcctacct cagcctccca 2340
agtagcttgg actacagggg tgtaccacca tgcccggcta attacatgtg ccagattcaa 2400
cccacgttcc agggttccaa acaaccaagg ctctatcatc ctgtcttaac aaatatacct 2460
tcataaagac ctggaaggca ggttgaaatg tggaattctt ggacttcttt cagttctacg 2520
tagaagggta gcagtggaga gctggctgcc tgcccgcccc tggcctttcc tcctttcccc 2580
acccctgctc cttgtggcac tgggcagggc ctacgttcaa ggctagcagt gtactcaaca 2640
agggacagtc cctgtgtggc ctgttcagga tcctatacac aggctcaggg ctctttgggc 2700
aggaaattcc aggatccggg tactcaagtg gtgttctaaa cagtggttct tggccgggtg 2760
tggtggctca cacctgtaat cccagcactt tgggaggccg aggctggcag atcacttgag 2820
gtcaggagtt cgagaccagc ctggccaaca tggtgaaacc ccatctctac taaaaataca 2880
aaaacttagc caggcatggt gtgcacgcct gtagtcccag ctactcggga ggctgaggca 2940
ggagaatcac ttgaacccag caggcggagg ttgcagtgag ctgagattgc accactgcac 3000
tccagcctgg tgacagagtg agactccata tcaaaataaa tacataaata aataaaaaca 3060
gtgattctta actgggagtg atttggcaac gtctggaatt atttttggtt atcccagcct 3120
ggcagggagg gacagggtat tactggcatc tagtgagtag gggctaggga ttctactgaa 3180
catcctacag tgtacaggac agcctccaca gcaaagaact gtctggccca aaatgtccat 3240
agtgcccaca ttcgatgccc tgcattagga agatataaat actcttaaat atcacagagt 3300
taaattcctt acccctgttc tagcagagat gatattcttg cggggggagc atcttcttgg 3360
cttcaacaca ttcttttctc catgggagat gatgccagaa gagggacaga acagggccca 3420
gtaaagcatg gggcctgggg ccagggaccc ccttgttcag gtgtgacgac catcctacga 3480
aggcaccacc caggcatcat tagaccgtct caaaagaaga gtaattcact gtcccaaagc 3540
agctctctcg tgtctgtggg cggatccctt ggcaagttta caatgaactg aaatctgccg 3600
aacttcctgg aacccaaaga aactttagcc ttgggcaaag gccctttggc cagcatttgc 3660
actgtttatg caaccgttta gaatatacga attatctgga gactactacc aaatacaaca 3720
ggcaaaactg caaatatgta tacttcctag aggatgataa aaaaatgtga attgtatttc 3780
tctgatagag gatgcattag agtctgaggg tctaaatagc gtaaataata aataagtaaa 3840
taaatcgata gtagtgtact ccaaacgagg ctggaatagc ttctattgtt gtttcacact 3900
ggacttcaat taagtctcag tattttgcca tactcaatat taagtactag gctggacgtg 3960
gtggctcatg tctgtaatcc cagcactttg ggaggccgag gtgggtagat ggctggcttg 4020
agctcaggag tttgaaacca gcctgggcaa catggtaaaa ccccatctgt acccaaaata 4080
caaaaatcag ccaggtgtgg tggcacatgc ctgtggtccc aggtacttgg gaggctgagg 4140
caggaggatg gcttgaaccc aggaggtgga ggctgcagtg agctatgatg gcgccactgc 4200
actccagcct gggtgacaga gcgagaccct gtctcaaaaa tcaaacaaac aaccccctcg 4260
ccccggacaa aagtagtttg cactattttc tcatttcaca atatgttttt gaaatatttc 4320
ccttgaaagg taagtcatat ttatcattcc tgttgtatgg aggcatcata aattatttca 4380
ccattctacc ctccttgagt gttgtggcct ttaggccaga caaaaacgca ggtgatgcct 4440
agaagccaac tagttgccgt ttggttatct gtagggttgt ggccttgcca aacaggaaaa 4500
atataaaaag aataccgaat tctgccaacc aaataagaaa ctctatacta aggactaaga 4560
aaattgcagg ggaagaaaag gtaagtcccg ggattgaggt gtagcgactt tctataccct 4620
cagaaaacta aaaaacaaga caaaaaaatg aaaactacaa aagcatccat cttggggcgt 4680
cccaattgct gagtaacaaa tgagacgctg tggccaaact cagtcataac taatgacatt 4740
tctagacaaa gtgacttcag attttcaaag cgtaccctgt ttacatcatt ttgccaattt 4800
cgcgtactgc aaccggcggg ccacgccccc gtgaaaagaa ggttgttttc tccacatttc 4860
ggggttctgg acgtttcccg gctgcggggc ggggggagtc tccggcgcac gcggcccctt 4920
ggccccgccc ccagtcattc ccggccactc gcgacccgag gctgccgcag ggggcgggct 4980
gagcgcgtgc gaggcgattg gtttggggcc agagtgggcg aggcgcggag gtctggccta 5040
taaagtagtc gcggagacgg ggtgctggtt tgcgtcgtag tctcctgcag cgtctggggt 5100
ttccgttgca gtcctcggaa ccaggacctc ggcgtggcct agcgagttat ggcgacgaag 5160
gccgtgtgcg tgctgaaggg cgacggccca gtgcagggca tcatcaattt cgagcagaag 5220
gcaagggctg ggacggaggc ttgtttgcga ggccgctccc acccgctcgt ccccccgcgc 5280
acctttgcta ggagcgggtc gcccgccagg cctcggggcc gccctggtcc agcgcccggt 5340
cccggcccgt gccgcccggt cggtgccttc gcccccagcg gtgcggtgcc caagtgctga 5400
gtcaccgggc gggcccgggc gcggggcgtg ggaccgaggc cgccgcgggg ctgggcctgc 5460
gcgtggcggg agcgcgggga gggattgccg cgggccgggg aggggcgggg gcgggcgtgc 5520
tgccctctgt ggtccttggg ccgccgccgc gggtctgtcg tggtgcctgg agcggctgtg 5580
ctcgtccctt gcttggccgt gttctcgttc ctgagggtcc cgcggacacc gagtggcgca 5640
gtgccaggcc cagcccgggg atggcgactg cgcctgggcc cgcctggtgt cttcgcatcc 5700
ctctccgctt tccggcttca gcgctctagg tcagggagtc ttcgcttttg tacagctcta 5760
aggctaggaa tggtttttat atttttaaaa ggctttggaa aacaaaaata cgcaacagag 5820
accgtttgtg tgacactttg cagggaagtt tgctggcctc tgttctaggt catgattggg 5880
ctgcaagggc agagaaggta gccttgaaca gaggtccttt tcctcctcct aagctccggg 5940
agccagaggt ttaactgacc cttttgggga tttttgaggg cagtgatctt aactttgggt 6000
gcacagttag cttatttgaa gatcttacta aaaatacacc agagcccaac ctccgaccaa 6060
ttacatcaaa acctgtccta gtgcagggtg agtattgctg ttttttgaaa gtttccaaaa 6120
gtgattttga tgtgcaccta cgattgagaa ctgtcgtttg aggacagtgg gtggagtttc 6180
gtatttggaa attagaagac ctggagtttc cattacaccg aattggcact taataactgt 6240
tgtcggagca tttcttaagc cacattttcg taaagtggct ttaaaattgc tctgccagta 6300
ggcaggttgc taagatggtc agagacaaac ttctgaacga ctcttgtaaa atatacagaa 6360
atattttcag aacttttatc agtaaaatta caaaacgtgt tgcaaggaag gtgcttgtga 6420
taacactgtc cccagaacct tagtgaagtt accaactggt ggaaaatttt ctcttgcact 6480
cggcttaaaa atcatgaggg aatatttact atacgaatga gattcagtct ttaaaggggt 6540
ttacagaaac gtgagaggac aggaacagtt agtctgtgta aatgtctgaa atatatgtga 6600
gggagataat gagtttagcc tttttcttta ataggtctcc agattttctg gaaaaggttc 6660
tttggcattt gactccattt tgctgtttca tttgtcagac ttctttttgt ccctctttac 6720
ttctccccac ataattcacc agtactagtg ttttgttttt cagaccaagt ctcgctctgt 6780
cgcccaggct ggagtgcagt ggcgcgatct cagctcactg caacctccgc ctcccaggtt 6840
caagcaattc tcctgcctca gcctcccggg tagctgggac tacaggcgcg cgccgccacg 6900
cctggctaat tttttatatt ttagtagaga cggcgtttca ccatgttggc caggatggtc 6960
tcgatctgtt gacgtcgtga tccacccgcc tcggcctccc aaagtgctgg gattacaggc 7020
gtgagccacc ccgcccggcc accagtgcta ttcttaagac gcctctgagg aatcccttct 7080
ccctggccat tgagaatcca tgcatgaacc caggttttcc accttccctg agcagcttgc 7140
atagttcctt cttttaagcg cctgacttcg ttttgtttgg tgcccgttgt acctgagaat 7200
gagccttgga tagtggagca ttccagcttt ccagatatgc agagataata cattggctat 7260
cagctacttg gcttggccta ttccgtgttt aaaatcttgg actctttgct agtttttaca 7320
gatcagaatt tttcacgtat taatccagtt ttcctagctt ctcttgaaga atttttggag 7380
atctcttcat actgagcctt cattagccca ggacagtact gctgtagcag ttcatatatt 7440
ttttcgcttc ccaggcctgt gttattcact taagttcata gcctggtccc tgcagggttg 7500
tacccgagca cagctactta gatgtcctga atgtattacc ggttaaatgg aggtttcaaa 7560
gaacctgctg tttttggccc tgtgctcttg ataacagagt gtttgaggga caactttcac 7620
atttgagttt ttccaaaatt aaaggttgta gaagagtcac agtatctatt gtcaaaaaga 7680
aaagaattta aaaaggcagc aattgccagg atacttcatt tgagcaatga tattttccag 7740
tggaaagtca catcttaagg gttaatgccc cttaactgtt ggccgtattt gaaaacaaac 7800
caagctaaaa acaagagaca ctgacatgtt gtatgacggt gtggtgtgga tgttgtgttt 7860
attttagtcc tgagatctag ttgtaacttc cttgatttct gtatgtagcc acggagcacc 7920
attacctgtc accattacct gaatggctat actgcttgct ttcattttgg tagagtggaa 7980
aggttaccta ggtttcagtg cttgaaaaga tttcagaaag cagtagtacg tctggttaga 8040
ctagaatcag tcctctcctg ggggcagtgg aatataatat tttctgactg ctaattaaaa 8100
atacctgtga tagccgggcg tggtggctta cgcctgtaat cccagcactt tgggaggccg 8160
agacgggtgg atcacgaggt cagcagatgg agaccatcct ggctaacacg gtgaaacccc 8220
gtctctacta aaaatgcaaa aaaattagcc gggtgtggtg gtgggcgcct gtagtcccag 8280
ctactcagga ggctgaggca ggagaatggc atgaacctgg gaggcggagc ttgcagtgag 8340
ccgagatcat gtcactgcac tccagcctgg gcgacagagc gagactcgtc tcaaaaaaaa 8400
aaagaaaaaa acttatgatg gacacttaaa aacactcact gagtggggag tggagagcag 8460
gggtcccagg gtagcctgtt ggacatttcc agggcgactt tttctttttt tttttttaaa 8520
gtcaagtgag tatgccatat ggaaaagggt gtgcgtggag aaaaagcaag gggctccaga 8580
gtgtaggatg agacatacac cttttgggtt aaaaaggctg aggcaggaga atggcgtgaa 8640
cccgggaggc ggagcttgca gtgagctgag atcatgccac tgcactccag cctgggcgac 8700
agagcgagac tcttgtctca aaataaaaaa cgtttacatg tacatgtata ttcaacatgt 8760
acaaatataa cctattcaaa agtatttact acataaatag gtacttacat tacctattta 8820
ctgtaatagt caaagcctat gaagtatcta acactgatgt gtaggtactc actttgcttg 8880
ccactctatt aggtgctttt tatgttattt aatcatgaag cctggccaca gggtgcttgt 8940
gcattgagtg tgggaacaag attaccatct cccttttgag gacacaggcc tagagcagtt 9000
aagcagcttg ctggaggttc actggctaga aagtggtcag cctgggattt ggacacagat 9060
ttttccactc ccaagtctgg ctgcttttta cttcactgtg aggggtaaag gtaaatcagc 9120
tgttttcttt gttcagaaac tctctccaac tttgcacttt tcttaaagga aagtaatgga 9180
ccagtgaagg tgtggggaag cattaaagga ctgactgaag gcctgcatgg attccatgtt 9240
catgagtttg gagataatac agcaggtggg tgttgtgctg tgctggtgac ccatacttgt 9300
tcaccctagt tagataaaca gtagagtagc ccctaaacgt taaaacccct caacttgttt 9360
ttgtttttga gaaagggtct tgctctgtcg ctcaggctgg agtgcagtgg cgctgtgcga 9420
tcatggctga ccttagcctt gacctcccag gctccattga tcctcatgcc ttggcccgta 9480
gctgggacta caggtacaca ccaccacgcc tggctaattt ttgtattttt ttctagaggt 9540
ggggtttcat catgttgccc aggctggtct tgaactgctg ggctcaagtg gtctatcctc 9600
ctcgacctcc caaagtgctg ggattacatg tgtgagccac tgtgcctggg aaaaccctca 9660
acttttcttt taaaaaagag gtcaacttta ttgtatataa gcactgtgct aaaattgcag 9720
gaactgggac catatcctga tttttgtaat aatgccagca gagtacacac aagaaaagta 9780
actgcactag attgtgaaga ctggggtgga cctgcttctg aaggtccagt gccctttgtc 9840
ttaagatttg gtgtagtgtg tctttagaaa ccaaaaaaag agaagaagat caaccttaag 9900
attagccaca aaactgggct ttgataccta ggtgtggaaa agaaagggaa agagttgatg 9960
ttttgtctta cagcatcatt gtagaagagg gtgttttttt gtttgtttgt tttttgagac 10020
ggagtcttac tctgtggccc aggctggagt gcagtggcgc gatctcggct cactgcaagc 10080
tccgcctccc gggttcatgc cattctcctg cctcagcccc ctgagtagct gggactacag 10140
gtgcccgcca ccccgcctgg ctaatttttt gtatttttag tagagacggg gtttcactgt 10200
gttagccaag atggtctctc tcctgacctc gtgatccgcc tgtctcagcc tcccaaagtg 10260
ctgggattac aggcatgagc caccgcaccc agccagaaga gggtgttttt taaagaaggc 10320
aaataggaaa taaaaacttg ggctcttaac ttttgtaatg atcccaggtg tttgagctgg 10380
gggttgaggg tgggtgcctc gagcaaaggg gctgcattta tttgcataat gccatgtaag 10440
agtagctcta caccccaaac acaggcttct tagtgggacc aaagtatgat acaaactgaa 10500
gatggaatgc agaggattat tggtactttg gaatatgctt aaaaaaaatt tttttaaagt 10560
atttttaaaa aatcaggcaa cccctgaacc agagtaggtt cagagaaact gccaaatttt 10620
attttcttaa tttgggattg gaagcaagtt aacagaagtt tatgagttaa gttgcattta 10680
gtgatctttt gccatatttg agtaataatc tgattttttt gtttatagat ttcttcttaa 10740
attaacttta ttcatcttgc taatttagtt tcaaatagtg atttgtaatg atcagatttg 10800
atccatttct gtaattgctg aaattccccc gagttgcttt ttggctttac cgcctctggt 10860
ctgggaggtg attgctctgc tgcttcctgt aacttgcctg cctttctccc tgtgtgggac 10920
tcctgcgggt gagagcgtgg ctgaagacag ccgtgttatg aaagggcctc ctgtgctgtc 10980
gaggttgtgc tctgtgaatg tcatcccctg gtgcacagca gcaccttcta cacaggatac 11040
agttggaatg ccgccccctc gagttgtgta aggcagcagc cttggccctt gcacataaga 11100
tgctgttgaa tattctgcct gcaccaagta aagggcacag atagaactgc ttggcatatg 11160
ttgctgggga gatgagtttt ttgtaaagta tactacgttc ttaagaattt ggatcataac 11220
catgggattt taataataga aaaactgttg aagatcagtc tggtccctta tttttacagt 11280
gaagaagcca aagcccagag aagggtgtta actttacaag tgtcagacag tagttagaac 11340
ttggtggggt tttttttttt ttttttttga gatggagtct tgctctgttg cccaggctgg 11400
agtgcagtgg tgcgatctca gctcactgca acctctgcct cccaggttca agcgattctc 11460
ctgcctcagc ctactaagta gctgggacta taggtgcgca ccaccacgcc tagctaattt 11520
ttgtattttt tcagtagaga cagggttttg ctatgctggc caggctggtc tcaaactcct 11580
gacctcagat gatccagcca cctcagcttc ccaaagtgct ggggttccag gtgttagcca 11640
ccatgcctgg ccatagactt gtttctgttc ccttctcact gtggctgtac caaggtgttg 11700
cttatcccag aagtcgtgat gcaggtcagc actttctcca tgggaagttt tagcagtgtt 11760
tctttttaga atgtatttgg gaactttaat tcataattta gctttttttt cttcttctta 11820
taaataggct gtaccagtgc aggtcctcac tttaatcctc tatccagaaa acacggtggg 11880
ccaaaggatg aagagaggta acaagatgct taactcttgt aataatggcg atagctttct 11940
ggagttcata tggtatacta cttgtaaata tgtgctaaga taattccgtg tttcccccac 12000
ctttgctttt gaacttgctg actcatctaa acccctgctc ccaaatgctg gaatgctttt 12060
acttcctggg cttaaaggaa ttgacaaatg gggacactta aaacgatttg gttttgtagc 12120
atttattgaa tatagaacta atacaagtgc caaaggggaa ctaatacagg aaatgtcatg 12180
aacagtactg tcaaccacta gcaaaatcaa tcatcattgt gaaacatagg aagcttctgt 12240
agataaaaaa aaaaattgat actgaaaact agtcgagact ccatttatat gtgtatgttt 12300
tctgaaagcc tttcagaaaa atattaaatt taaggacaag atttttatat cagaggcctt 12360
gggacatagc tttgttagct atgccagtaa ttaacaggca taactcagta actgagagtt 12420
taccctttgg tacttctgaa atcaggtgca gccccatctt tcttcccaga gcattagtgt 12480
gtagacgtga agccttgttt gaagagctgt atttagaatg cctagctact tgtttgcaaa 12540
tttgtgtcta ctcagtcaag ttttaattta gctcatgaac taccttgatg tttagtggca 12600
tcagccctaa tccatctgat gctttttcat tattaggcat gttggagact tgggcaatgt 12660
gactgctgac aaagatggtg tggccgatgt gtctattgaa gattctgtga tctcactctc 12720
aggagaccat tgcatcattg gccgcacact ggtggtaagt tttcataaaa ggatatgcat 12780
aaaacttctt ctaacataca gtcatgtatc ttttcacttt gattgttagt cgcggtttct 12840
aaagatccag ataaactgta cttgcagttc aaattaggaa aagcaatttt attggacaat 12900
tacggtgaaa atgaattatt ttatctaggt cagttaagaa cactgttctg ctaagatgca 12960
gtaaaaagca ggttacattt gaccatatta gatctgagtt tggaaaacag aagtagtctt 13020
tagttttaaa atggccagat tttcttgcca ggattgggtt tctcacttgt taaacagaac 13080
attttgttaa gtttaaaacc tgggatggac ttaagtattc atgttcattc atgttcattc 13140
aggactgcag gttatcatga cttgtttaac ttgtgggaag ctgttgtccc aagttatcct 13200
ggggaactgc atctggttct tgcaaaacac caagtagaca ggctctcttt tacctcccct 13260
tgagggcatt aacattcagt agtcacttcc attcagttaa ccctttattt ttatggtttt 13320
tcttgagcca tagttgtaaa gcagaaaaat catttataaa ggtttgttga acaaaattca 13380
aaatactgtt gcttaaagta ttaagatttt ttaggattat accttactta taggcccgtc 13440
attcatttgg catgaaattt tgagttttat tcactttcac tttccttttt ttccaaagca 13500
attaaaaaaa ctgccaaagt aagagtgact gcggaactaa ggttactgta acttaccatg 13560
gaggattaag ggtagcgtgt ggtggtctac aacatagtta tttgggtttt agtatttcat 13620
ttagacagca acacttacct aatgtttaaa ggtaatgtct ttgcaacacc aagaaaaagc 13680
tttgagtagt agtttctact tttaaactac taaatattag tatatctctc tactaggatt 13740
aatgttattt ttctaatatt atgaggttct taaacatctt ttgggtattg ttgggaggag 13800
gtagtgatta cttgacagcc caaagttatc ttcttaaaat tttttacagg tccatgaaaa 13860
agcagatgac ttgggcaaag gtggaaatga agaaagtaca aagacaggaa acgctggaag 13920
tcgtttggct tgtggtgtaa ttgggatcgc ccaataaaca ttcccttgga tgtagtctga 13980
ggccccttaa ctcatctgtt atcctgctag ctgtagaaat gtatcctgat aaacattaaa 14040
cactgtaatc ttaaaagtgt aattgtgtga ctttttcaga gttgctttaa agtacctgta 14100
gtgagaaact gatttatgat cacttggaag atttgtatag ttttataaaa ctcagttaaa 14160
atgtctgttt caatgacctg tattttgcca gacttaaatc acagatgggt attaaacttg 14220
tcagaatttc tttgtcattc aagcctgtga ataaaaaccc tgtatggcac ttattatgag 14280
gctattaaaa gaatccaaat tcaaactaaa ttagctctga tacttattta tataaacagc 14340
ttcagtggaa cagatttagt aatactaaca gtgatagcat tttattttga aagtgttttg 14400
agaccatcaa aatgcatact ttaaaacagc aggtctttta gctaaaacta acacaactct 14460
gcttagacaa ataggctgtc ctttgaaagc tttagggaaa tgttcctgct tagtcatttt 14520
agcattttga ttcataaagt acctcctcat tttaaaaaga cattatgatg taagagagcc 14580
atttgataac tttttagtga gctttgaaag gcaagttaca gcctcagcta gctagtaaga 14640
ttatctacct gccagaatgg cacaaattct acattcaagg gtagacgctg gcacaaccta 14700
cttacagatt agccctttaa agcaatctgt agcattagaa gatggaacca aggaaatgtt 14760
tgactgtggg ttctggctgt tgagaaataa tttacacacc gaattagtga aatgagtcac 14820
tttctcttaa tgtatttatg tacctgagag aatgcttttc aatgttaacc taactcaggt 14880
ttgactaaat tattcaattg gaaattgtag aatattattt ctgataaacc agaaataagt 14940
gaaatgctgt ttgttcataa atatgtactt tatcaaatgt aggagagatc atttaggaga 15000
ggaaaagcta aattggaaga caaatctgta gtgtttccaa agttttaaaa ttatggtaaa 15060
caacagtatg ttcacagtaa gtggttaaaa caaccattct ttaaatctca gtagagaatt 15120
tttaaaaagc agtatttaac acatttccct aatgtagttt gttgcctatg tggaataact 15180
caattagaga ctcacttatg ccttttgaaa cttcaaatat aattacacta ccagttttta 15240
catgtgcata taggatggtc ccaatacttt aaattggaaa tacaggctgt aagtccttca 15300
agtctggatg ttgggtaatc acgttttctt ccagaagcca tttgttagga ctttaaaact 15360
tctcagtggg ccagtgtaaa attaaggaca agttttataa tttaaattta cagataaata 15420
taaaacaatt ttctctcatt ttctaaaggc aggaatataa ggacattgcc ctagatatat 15480
tctccccatc aaaccaaagg tcttgctgct gagtattatt taaaaaccag agtaataaag 15540
cagcttcgcc tgaggatgaa ggcaaagaca aagttaactg ctcagcatac tgaaaccagg 15600
agtttgaaaa agtaattcaa aacaacttca aggccataaa tacttggata gtgtgacatc 15660
aggtcttggc actggatttc ctgcaatttc agatgaaggc ttgacttggc tttagatgtt 15720
ttcatgtgat aattcttgga taacctacaa cgatttttcc tatttaaccc accaacttta 15780
agcaaaagaa agaacgtata tgtgggggaa aagttcgttt acctctgccc cgcaggggaa 15840
ttaaaacgct ggtgaagaaa ggcaacaggc aaggcttata taaggaaaca gtagtaggct 15900
gcactgaagt cctcaaacac aacaaaaagc tcttaggttg caaatgttaa ccttgattct 15960
tttacccttt tgaaaaattc aatgggatgg ttggaaaaaa aaaaaaccac agacacacac 16020
acacacacac gcaaccttct aacgtaatac ccaggcagtc cgataattta tagtacaacg 16080
tgtaacactg ggatccaact tttcacccag caaaatctcc ttacaaatta gggcaacata 16140
taccacaaag ccaatggaaa aaaaaagaaa acctcgattg aattgcaaac acagcttttc 16200
aattgacatt aaaacaacta acctttacct tatgactgag cactaaaaat caaaagtatt 16260
acatatgaaa gtgagaataa ctacataaaa tgtctatttt catcaaataa 16310
<210> 58
<211> 6706
<212> DNA
<213> Intelligent (Homo sapiens)
<400> 58
agagtcatcc agctggagcc ctgagtggct gagctcaggc cttcgcagca ttcttgggtg 60
ggagcagcca cgggtcagcc acaagggcca cagccatgaa tggcacagaa ggccctaact 120
tctacgtgcc cttctccaat gcgacgggtg tggtacgcag ccccttcgag tacccacagt 180
actacctggc tgagccatgg cagttctcca tgctggccgc ctacatgttt ctgctgatcg 240
tgctgggctt ccccatcaac ttcctcacgc tctacgtcac cgtccagcac aagaagctgc 300
gcacgcctct caactacatc ctgctcaacc tagccgtggc tgacctcttc atggtcctag 360
gtggcttcac cagcaccctc tacacctctc tgcatggata cttcgtcttc gggcccacag 420
gatgcaattt ggagggcttc tttgccaccc tgggcggtat gagccgggtg tgggtggggt 480
gtgcaggagc ccgggagcat ggaggggtct gggagagtcc cgggcttggc ggtggtggct 540
gagaggcctt ctcccttctc ctgtcctgtc aatgttatcc aaagccctca tatattcagt 600
caacaaacac cattcatggt gatagccggg ctgctgtttg tgcagggctg gcactgaaca 660
ctgccttgat cttatttgga gcaatatgcg cttgtctaat ttcacagcaa gaaaactgag 720
ctgaggctca aagaagtcaa gcgccctgct ggggcgtcac acagggacgg gtgcagagtt 780
gagttggaag cccgcatcta tctcgggcca tgtttgcagc accaagcctc tgtttccctt 840
ggagcagctg tgctgagtca gacccaggct gggcactgag ggagagctgg gcaagccaga 900
cccctcctct ctgggggccc aagctcaggg tgggaagtgg attttccatt ctccagtcat 960
tgggtcttcc ctgtgctggg caatgggctc ggtcccctct ggcatcctct gcctcccctc 1020
tcagcccctg tcctcaggtg cccctccagc ctccctgccg cgttccaagt ctcctggtgt 1080
tgagaaccgc aagcagccgc tctgaagcag ttcctttttg ctttagaata atgtcttgca 1140
tttaacagga aaacagatgg ggtgctgcag ggataacaga tcccacttaa cagagaggaa 1200
aactgaggca gggagagggg aagagactca tttagggatg tggccaggca gcaacaagag 1260
cctaggtctc ctggctgtga tccaggaata tctctgctga gatgcaggag gagacgctag 1320
aagcagccat tgcaaagctg ggtgacgggg agagcttacc gccagccaca agcgtctctc 1380
tgccagcctt gccctgtctc ccccatgtcc aggctgctgc ctcggtccca ttctcaggga 1440
atctctggcc attgttgggt gtttgttgca ttcaataatc acagatcact cagttctggc 1500
cagaaggtgg gtgtgccact tacgggtggt tgttctctgc agggtcagtc ccagtttaca 1560
aatattgtcc ctttcactgt taggaatgtc ccagtttggt tgattaacta tatggccact 1620
ctccctatgg aacttcatgg ggtggtgagc aggacagatg tctgaattcc atcatttcct 1680
tcttcttcct ctgggcaaaa cattgcacat tgcttcatgg ctcctaggag aggcccccac 1740
atgtccgggt tatttcattt cccgagaagg gagagggagg aaggactgcc aattctgggt 1800
ttccaccacc tctgcattcc ttcccaacaa ggaactctgc cccacattag gatgcattct 1860
tctgctaaac acacacacac acacacacac acacaacaca cacacacaca cacacacaca 1920
cacacacaca aaactcccta ccgggttccc agttcaatcc tgaccccctg atctgattcg 1980
tgtcccttat gggcccagag cgctaagcaa ataacttccc ccattccctg gaatttcttt 2040
gcccagctct cctcagcgtg tggtccctct gccccttccc cctcctccca gcaccaagct 2100
ctctccttcc ccaaggcctc ctcaaatccc tctcccactc ctggttgcct tcctagctac 2160
cctctccctg tctagggggg agtgcaccct ccttaggcag tggggtctgt gctgaccgcc 2220
tgctgactgc cttgcaggtg aaattgccct gtggtccttg gtggtcctgg ccatcgagcg 2280
gtacgtggtg gtgtgtaagc ccatgagcaa cttccgcttc ggggagaacc atgccatcat 2340
gggcgttgcc ttcacctggg tcatggcgct ggcctgcgcc gcacccccac tcgccggctg 2400
gtccaggtaa tggcactgag cagaagggaa gaagctccgg gggctctttg tagggtcctc 2460
cagtcaggac tcaaacccag tagtgtctgg ttccaggcac tgaccttgta tgtctcctgg 2520
cccaaatgcc cactcagggt aggggtgtag ggcagaagaa gaaacagact ctaatgttgc 2580
tacaagggct ggtcccatct cctgagcccc atgtcaaaca gaatccaaga catcccaacc 2640
cttcaccttg gctgtgcccc taatcctcaa ctaagctagg cgcaaattcc aatcctcttt 2700
ggtctagtac cccgggggca gccccctcta accttgggcc tcagcagcag gggaggccac 2760
accttcctag tgcaggtggc catattgtgg ccccttggaa ctgggtccca ctcagcctct 2820
aggcgattgt ctcctaatgg ggctgagatg agacacagtg gggacagtgg tttggacaat 2880
aggactggtg actctggtcc ccagaggcct catgtccctc tgtctccaga aaattcccac 2940
tctcacttcc ctttcctcct cagtcttgct agggtccatt tcttacccct tgctgaattt 3000
gagcccaccc cctggacttt ttccccatct tctccaatct ggcctagttc tatcctctgg 3060
aagcagagcc gctggacgct ctgggtttcc tgaggcccgt ccactgtcac caatatcagg 3120
aaccattgcc acgtcctaat gacgtgcgct ggaagcctct agtttccaga agctgcacaa 3180
agatccctta gatactctgt gtgtccatct ttggcctgga aaatactctc accctggggc 3240
taggaagacc tcggtttgta caaacttcct caaatgcaga gcctgagggc tctccccacc 3300
tcctcaccaa ccctctgcgt ggcatagccc tagcctcagc gggcagtgga tgctggggct 3360
gggcatgcag ggagaggctg ggtggtgtca tctggtaacg cagccaccaa acaatgaagc 3420
gacactgatt ccacaaggtg catctgcatc cccatctgat ccattccatc ctgtcaccca 3480
gccatgcaga cgtttatgat ccccttttcc agggagggaa tgtgaagccc cagaaagggc 3540
cagcgctcgg cagccacctt ggctgttccc aagtccctca caggcagggt ctccctacct 3600
gcctgtcctc aggtacatcc ccgagggcct gcagtgctcg tgtggaatcg actactacac 3660
gctcaagccg gaggtcaaca acgagtcttt tgtcatctac atgttcgtgg tccacttcac 3720
catccccatg attatcatct ttttctgcta tgggcagctc gtcttcaccg tcaaggaggt 3780
acgggccggg gggtgggcgg cctcacggct ctgagggtcc agcccccagc atgcatctgc 3840
ggctcctgct ccctggagga gccatggtct ggacccgggt cccgtgtcct gcaggccgct 3900
gcccagcagc aggagtcagc caccacacag aaggcagaga aggaggtcac ccgcatggtc 3960
atcatcatgg tcatcgcttt cctgatctgc tgggtgccct acgccagcgt ggcattctac 4020
atcttcaccc accagggctc caacttcggt cccatcttca tgaccatccc agcgttcttt 4080
gccaagagcg ccgccatcta caaccctgtc atctatatca tgatgaacaa gcaggtgcct 4140
actgcgggtg ggagggcccc agtgccccag gccacaggcg ctgcctgcca aggacaagct 4200
acttcccagg gcaggggagg gggctccatc agggttactg gcagcagtct tgggtcagca 4260
gtcccaatgg ggagtgtgtg agaaatgcag attcctggcc ccactcagaa ctgctgaatc 4320
tcagggtggg cccaggaacc tgcatttcca gcaagccctc cacaggtggc tcagatgctc 4380
actcaggtgg gagaagctcc agtcagctag ttctggaagc ccaatgtcaa agtcagaagg 4440
acccaagtcg ggaatgggat gggccagtct ccataaagct gaataaggag ctaaaaagtc 4500
ttattctgag gggtaaaggg gtaaagggtt cctcggagag gtacctccga ggggtaaaca 4560
gttgggtaaa cagtctctga agtcagctct gccattttct agctgtatgg ccctgggcaa 4620
gtcaatttcc ttctctgtgc tttggtttcc tcatccatag aaaggtagaa agggcaaaac 4680
accaaactct tggattacaa gagataattt acagaacacc cttggcacac agagggcacc 4740
atgaaatgtc acgggtgaca cagccccctt gtgctcagtc cctggcatct ctaggggtga 4800
ggagcgtctg cctagcaggt tccctccagg aagctggatt tgagtggatg gggcgctgga 4860
atcgtgaggg gcagaagcag gcaaagggtc ggggcgaacc tcactaacgt gccagttcca 4920
agcacactgt gggcagccct ggccctgact caagcctctt gccttccagt tccggaactg 4980
catgctcacc accatctgct gcggcaagaa cccactgggt gacgatgagg cctctgctac 5040
cgtgtccaag acggagacga gccaggtggc cccggcctaa gacctgccta ggactctgtg 5100
gccgactata ggcgtctccc atcccctaca ccttccccca gccacagcca tcccaccagg 5160
agcagcgcct gtgcagaatg aacgaagtca cataggctcc ttaatttttt tttttttttt 5220
aagaaataat taatgaggct cctcactcac ctgggacagc ctgagaaggg acatccacca 5280
agacctactg atctggagtc ccacgttccc caaggccagc gggatgtgtg cccctcctcc 5340
tcccaactca tctttcagga acacgaggat tcttgctttc tggaaaagtg tcccagctta 5400
gggataagtg tctagcacag aatggggcac acagtaggtg cttaataaat gctggatgga 5460
tgcaggaagg aatggaggaa tgaatgggaa gggagaacat atctatcctc tcagaccctc 5520
gcagcagcag caactcatac ttggctaatg atatggagca gttgtttttc cctccctggg 5580
cctcactttc ttctcctata aaatggaaat cccagatccc tggtcctgcc gacacgcagc 5640
tactgagaag accaaaagag gtgtgtgtgt gtctatgtgt gtgtttcagc actttgtaaa 5700
tagcaagaag ctgtacagat tctagttaat gttgtgaata acatcaatta atgtaactag 5760
ttaattacta tgattatcac ctcctgatag tgaacatttt gagattgggc attcagatga 5820
tggggtttca cccaaccttg gggcaggttt ttaaaaatta gctaggcatc aaggccagac 5880
cagggctggg ggttgggctg taggcaggga cagtcacagg aatgcagaat gcagtcatca 5940
gacctgaaaa aacaacactg ggggaggggg acggtgaagg ccaagttccc aatgagggtg 6000
agattgggcc tggggtctca cccctagtgt ggggccccag gtcccgtgcc tccccttccc 6060
aatgtggcct atggagagac aggcctttct ctcagcctct ggaagccacc tgctcttttg 6120
ctctagcacc tgggtcccag catctagagc atggagcctc tagaagccat gctcacccgc 6180
ccacatttaa ttaacagctg agtccctgat gtcatcctta tctcgaagag cttagaaaca 6240
aagagtggga aattccactg ggcctacctt ccttggggat gttcatgggc cccagtttcc 6300
agtttccctt gccagacaag cccatcttca gcagttgcta gtccattctc cattctggag 6360
aatctgctcc aaaaagctgg ccacatctct gaggtgtcag aattaagctg cctcagtaac 6420
tgctccccct tctccatata agcaaagcca gaagctctag ctttacccag ctctgcctgg 6480
agactaaggc aaattgggcc attaaaagct cagctcctat gttggtatta acggtggtgg 6540
gttttgttgc tttcacactc tatccacagg atagattgaa actgccagct tccacctgat 6600
ccctgaccct gggatggctg gattgagcaa tgagcagagc caagcagcac agagtcccct 6660
ggggctagag gtggaggagg cagtcctggg aatgggaaaa acccca 6706
<210> 59
<211> 27321
<212> DNA
<213> Intelligent (Homo sapiens)
<400> 59
acgtaaccta cggtgtcccg ctaggaaaga gaggtgcgtc aaacagcgac aagttccgcc 60
cacgtaaaag atgacgcttg gtgtgtcagc cgtccctgct gcccggttgc ttctcttttg 120
ggggcggggt ctagcaagag caggtgtggg tttaggaggt gtgtgttttt gtttttccca 180
ccctctctcc ccactacttg ctctcacagt actcgctgag ggtgaacaag aaaagacctg 240
ataaagatta accagaagaa aacaaggagg gaaacaaccg cagcctgtag caagctctgg 300
aactcaggag tcgcgcgcta ggggccgggg ccggggccgg ggcgtggtcg gggcgggccc 360
gggggcgggc ccggggcggg gctgcggttg cggtgcctgc gcccgcggcg gcggaggcgc 420
aggcggtggc gagtgggtga gtgaggaggc ggcatcctgg cgggtggctg tttggggttc 480
ggctgccggg aagaggcgcg ggtagaagcg ggggctctcc tcagagctcg acgcattttt 540
actttccctc tcatttctct gaccgaagct gggtgtcggg ctttcgcctc tagcgactgg 600
tggaattgcc tgcatccggg ccccgggctt cccggcggcg gcggcggcgg cggcggcgca 660
gggacaaggg atggggatct ggcctcttcc ttgctttccc gccctcagta cccgagctgt 720
ctccttcccg gggacccgct gggagcgctg ccgctgcggg ctcgagaaaa gggagcctcg 780
ggtactgaga ggcctcgcct gggggaaggc cggagggtgg gcggcgcgcg gcttctgcgg 840
accaagtcgg ggttcgctag gaacccgaga cggtccctgc cggcgaggag atcatgcggg 900
atgagatggg ggtgtggaga cgcctgcaca atttcagccc aagcttctag agagtggtga 960
tgacttgcat atgagggcag caatgcaagt cggtgtgctc cccattctgt gggacatgac 1020
ctggttgctt cacagctccg agatgacaca gacttgctta aaggaagtga ctattgtgac 1080
ttgggcatca cttgactgat ggtaatcagt tgtctaaaga agtgcacaga ttacatgtcc 1140
gtgtgctcat tgggtctatc tggccgcgtt gaacaccacc aggctttgta ttcagaaaca 1200
ggagggaggt cctgcacttt cccaggaggg gtggcccttt cagatgcaat cgagattgtt 1260
aggctctggg agagtagttg cctggttgtg gcagttggta aatttctatt caaacagttg 1320
ccatgcacca gttgttcaca acaagggtac gtaatctgtc tggcattact tctacttttg 1380
tacaaaggat caaaaaaaaa aaagatactg ttaagatatg atttttctca gactttggga 1440
aacttttaac ataatctgtg aatatcacag aaacaagact atcatatagg ggatattaat 1500
aacctggagt cagaatactt gaaatacggt gtcatttgac acgggcattg ttgtcaccac 1560
ctctgccaag gcctgccact ttaggaaaac cctgaatcag ttggaaactg ctacatgctg 1620
atagtacatc tgaaacaaga acgagagtaa ttaccacatt ccagattgtt cactaagcca 1680
gcatttacct gctccaggaa aaaattacaa gcaccttatg aagttgataa aatattttgt 1740
ttggctatgt tggcactcca caatttgctt tcagagaaac aaagtaaacc aaggaggact 1800
tctgtttttc aagtctgccc tcgggttcta ttctacgtta attagatagt tcccaggagg 1860
actaggttag cctacctatt gtctgagaaa cttggaactg tgagaaatgg ccagatagtg 1920
atatgaactt caccttccag tcttccctga tgttgaagat tgagaaagtg ttgtgaactt 1980
tctggtactg taaacagttc actgtccttg aagtggtcct gggcagctcc tgttgtggaa 2040
agtggacggt ttaggatcct gcttctcttt gggctgggag aaaataaaca gcatggttac 2100
aagtattgag agccaggttg gagaaggtgg cttacacctg taatgccaga gctttgggag 2160
gcggaggcaa gaggatcact tgaagccagg agttcaagct caacctgggc aacgtagacc 2220
ctgtctctac aaaaaattaa aaacttagcc gggcgtggtg atgtgcacct gtagtcctag 2280
ctacttggga ggctgaggca ggagggtcat ttgagcccaa gagtttgaag ttaccgagag 2340
ctatgatcct gccagtgcat tccagcctgg atgacaaaac gagaccctgt ctctaaaaaa 2400
caagaagtga gggctttatg attgtagaat tttcactaca atagcagtgg accaaccacc 2460
tttctaaata ccaatcaggg aagagatggt tgatttttta acagacgttt aaagaaaaag 2520
caaaacctca aacttagcac tctactaaca gttttagcag atgttaatta atgtaatcat 2580
gtctgcatgt atgggattat ttccagaaag tgtattggga aacctctcat gaaccctgtg 2640
agcaagccac cgtctcactc aatttgaatc ttggcttccc tcaaaagact ggctaatgtt 2700
tggtaactct ctggagtaga cagcactaca tgtacgtaag ataggtacat aaacaactat 2760
tggttttgag ctgatttttt tcagctgcat ttgcatgtat ggatttttct caccaaagac 2820
gatgacttca agtattagta aaataattgt acagctctcc tgattatact tctctgtgac 2880
atttcatttc ccaggctatt tcttttggta ggatttaaaa ctaagcaatt cagtatgatc 2940
tttgtccttc attttctttc ttattctttt tgtttgtttg tttgtttgtt tttttcttga 3000
ggcagagtct ctctctgtcg cccaggctgg agtgcagtgg cgccatctca gctcattgca 3060
acctctgcca cctccgggtt caagagattc tcctgcctca gcctcccgag tagctgggat 3120
tacaggtgtc caccaccaca cccggctaat tttttgtatt tttagtagag gtggggtttc 3180
accatgttgg ccaggctggt cttgagctcc tgacctcagg tgatccacct gcctcggcct 3240
accaaagagc tgggataaca ggtgtgaccc accatgcccg gcccattttt tttttcttat 3300
tctgttagga gtgagagtgt aactagcagt ataatagttc aattttcaca acgtggtaaa 3360
agtttcccta taattcaatc agattttgct ccagggttca gttctgtttt aggaaatact 3420
tttattttca gtttaatgat gaaatattag agttgtaata ttgcctttat gattatccac 3480
ctttttaacc taaaagaatg aaagaaaaat atgtttgcaa tataatttta tggttgtatg 3540
ttaacttaat tcattatgtt ggcctccagt ttgctgttgt tagttatgac agcagtagtg 3600
tcattaccat ttcaattcag attacattcc tatatttgat cattgtaaac tgactgctta 3660
cattgtatta aaaacagtgg atattttaaa gaagctgtac ggcttatatc tagtgctgtc 3720
tcttaagact attaaattga tacaacatat ttaaaagtaa atattaccta aatgaatttt 3780
tgaaattaca aatacacgtg ttaaaactgt cgttgtgttc aaccatttct gtacatactt 3840
agagttaact gttttgccag gctctgtatg cctactcata atatgataaa agcactcatc 3900
taatgctctg taaatagaag tcagtgcttt ccatcagact gaactctctt gacaagatgt 3960
ggatgaaatt ctttaagtaa aattgtttac tttgtcatac atttacagat caaatgttag 4020
ctcccaaagc aatcatatgg caaagatagg tatatcatag tttgcctatt agctgctttg 4080
tattgctatt attataaata gacttcacag ttttagactt gcttaggtga aattgcaatt 4140
ctttttactt tcagtcttag ataacaagtc ttcaattata gtacaatcac acattgctta 4200
ggaatgcatc attaggcgat tttgtcatta tgcaaacatc atagagtgta cttacacaaa 4260
cctagatagt atagccttta tgtacctagg ccgtatggta tagtctgttg ctcctaggcc 4320
acaaacctgt acaactgtta ctgtactgaa tactatagac agttgtaaca cagtggtaaa 4380
tatttatcta aatatatgca aacagagaaa aggtacagta aaagtatggt ataaaagata 4440
atggtatacc tgtgtaggcc acttaccacg aatggagctt gcaggactag aagttgctct 4500
gggtgagtca gtgagtgagt ggtgaattaa tgtgaaggcc tagaacactg tacaccactg 4560
tagactataa acacagtacg ctgaagctac accaaattta tcttaacagt ttttcttcaa 4620
taaaaaatta taacttttta actttgtaaa ctttttaatt ttttaacttt taaaatactt 4680
agcttgaaac acaaatacat tgtatagcta tacaaaaata ttttttcttt gtatccttat 4740
tctagaagct tttttctatt ttctatttta aatttttttt tttacttgtt agtcgttttt 4800
gttaaaaact aaaacacaca cactttcacc taggcataga caggattagg atcatcagta 4860
tcactccctt ccacctcact gccttccacc tccacatctt gtcccactgg aaggttttta 4920
ggggcaataa cacacatgta gctgtcacct atgataacag tgctttctgt tgaatacctc 4980
ctgaaggact tgcctgaggc tgttttacat ttaacttaaa aaaaaaaaaa gtagaaggag 5040
tgcactctaa aataacaata aaaggcatag tatagtgaat acataaacca gcaatgtagt 5100
agtttattat caagtgttgt acactgtaat aattgtatgt gctatacttt aaataacttg 5160
caaaatagta ctaagacctt atgatggtta cagtgtcact aaggcaatag catattttca 5220
ggtccattgt aatctaatgg gactaccatc atatatgcag tctaccattg actgaaacgt 5280
tacatggcac ataactgtat ttgcaagaat gatttgtttt acattaatat cacataggat 5340
gtaccttttt agagtggtat gtttatgtgg attaagatgt acaagttgag caaggggacc 5400
aagagccctg ggttctgtct tggatgtgag cgtttatgtt cttctcctca tgtctgtttt 5460
ctcattaaat tcaaaggctt gaacgggccc tatttagccc ttctgttttc tacgtgttct 5520
aaataactaa agcttttaaa ttctagccat ttagtgtaga actctctttg cagtgatgaa 5580
atgctgtatt ggtttcttgg ctagcatatt aaatattttt atctttgtct tgatacttca 5640
atgtcgtttt aaacatcagg atcgggcttc agtattctca taaccagaga gttcactgag 5700
gatacaggac tgtttgccca ttttttgtta tggctccaga cttgtggtat ttccatgtct 5760
tttttttttt tttttttttt gaccttttag cggctttaaa gtatttctgt tgttaggtgt 5820
tgtattactt ttctaagatt acttaacaaa gcaccacaaa ctgagtggct ttaaacaaca 5880
gcaatttatt ctctcacaat tctagaagct agaagtccga aatcaaagtg ttgacagggg 5940
catgatcttc aagagagaag actctttcct tgcctcttcc tggcttctgg tggttaccag 6000
caatcctgag tgttcctttc ttgccttgta gtttcaacaa tccagtatct gccttttgtc 6060
ttcacatggc tgtctaccat ttgtctctgt gtctccaaat ctctctcctt ataaacacag 6120
cagttattgg attaggcccc actctaatcc agtatgaccc cattttaaca tgattacact 6180
tatttctaga taaggtcaca ttcacgtaca ccaagggtta ggaattgaac atatcttttt 6240
gggggacaca attcaaccca caagtgtcag tctctagctg agcctttccc ttcctgtttt 6300
tctccttttt agttgctatg ggttaggggc caaatctcca gtcatactag aattgcacat 6360
ggactggata tttgggaata ctgcgggtct attctatgag ctttagtatg taacatttaa 6420
tatcagtgta aagaagccct tttttaagtt atttctttga atttctaaat gtatgccctg 6480
aatataagta acaagttacc atgtcttgta aaatgatcat atcaacaaac atttaatgtg 6540
cacctactgt gctagttgaa tgtctttatc ctgataggag ataacaggat tccacatctt 6600
tgacttaaga ggacaaacca aatatgtcta aatcatttgg ggttttgatg gatatcttta 6660
aattgctgaa cctaatcatt ggtttcatat gtcattgttt agatatctcc ggagcatttg 6720
gataatgtga cagttggaat gcagtgatgt cgactctttg cccaccgcca tctccagctg 6780
ttgccaagac agagattgct ttaagtggca aatcaccttt attagcagct acttttgctt 6840
actgggacaa tattcttggt cctagagtaa ggcacatttg ggctccaaag acagaacagg 6900
tacttctcag tgatggagaa ataacttttc ttgccaacca cactctaaat ggagaaatcc 6960
ttcgaaatgc agagagtggt gctatagatg taaagttttt tgtcttgtct gaaaagggag 7020
tgattattgt ttcattaatc tttgatggaa actggaatgg ggatcgcagc acatatggac 7080
tatcaattat acttccacag acagaactta gtttctacct cccacttcat agagtgtgtg 7140
ttgatagatt aacacatata atccggaaag gaagaatatg gatgcataag gtaagtgatt 7200
tttcagctta ttaatcatgt taacctatct gttgaaagct tattttctgg tacatataaa 7260
tcttattttt ttaattatat gcagtgaaca tcaaacaata aatgttattt attttgcatt 7320
taccctatta gatacaaata catctggtct gatacctgtc atcttcatat taactgtgga 7380
aggtacgaaa tggtagctcc acattataga tgaaaagcta aagcttagac aaataaagaa 7440
acttttagac cctggattct tcttgggagc ctttgactct aatacctttt gtttcccttt 7500
cattgcacaa ttctgtcttt tgcttactac tatgtgtaag tataacagtt caaagtaata 7560
gtttcataag ctgttggtca tgtagccttt ggtctcttta acctctttgc caagttccca 7620
ggttcataaa atgaggaggt tgaatggaat ggttcccaag agaattcctt ttaatcttac 7680
agaaattatt gttttcctaa atcctgtagt tgaatatata atgctattta catttcagta 7740
tagttttgat gtatctaaag aacacattga attctccttc ctgtgttcca gtttgatact 7800
aacctgaaag tccattaagc attaccagtt ttaaaaggct tttgcccaat agtaaggaaa 7860
aataatatct tttaaaagaa taatttttta ctatgtttgc aggcttactt ccttttttct 7920
cacattatga aactcttaaa atcaggagaa tcttttaaac aacatcataa tgtttaattt 7980
gaaaagtgca agtcattctt ttcctttttg aaactatgca gatgttacat tgactgtttt 8040
ctgtgaagtt atcttttttt cactgcagaa taaaggttgt tttgatttta ttttgtattg 8100
tttatgagaa catgcatttg ttgggttaat ttcctacccc tgcccccatt ttttccctaa 8160
agtagaaagt atttttcttg tgaactaaat tactacacaa gaacatgtct attgaaaaat 8220
aagcaagtat caaaatgttg tgggttgttt ttttaaataa attttctctt gctcaggaaa 8280
gacaagaaaa tgtccagaag attatcttag aaggcacaga gagaatggaa gatcaggtat 8340
atgcaaattg catactgtca aatgtttttc tcacagcatg tatctgtata aggttgatgg 8400
ctacatttgt caaggccttg gagacatacg aataagcctt taatggagct tttatggagg 8460
tgtacagaat aaactggagg aagatttcca tatcttaaac ccaaagagtt aaatcagtaa 8520
acaaaggaaa atagtaattg catctacaaa ttaatatttg ctcccttttt ttttctgttt 8580
gcccagaata aattttggat aacttgttca tagtaaaaat aaaaaaaatt gtctctgata 8640
tgttctttaa ggtactactt ctcgaacctt tccctagaag tagctgtaac agaaggagag 8700
catatgtacc cctgaggtat ctgtctgggg tgtaggccca ggtccacaca atatttcttc 8760
taagtcttat gttgtatcgt taagactcat gcaatttaca ttttattcca taactatttt 8820
agtattaaaa tttgtcagtg atatttctta ccctctcctc taggaaaatg tgccatgttt 8880
atcccttggc tttgaatgcc cctcaggaac agacactaag agtttgagaa gcatggttac 8940
aagggtgtgg cttcccctgc ggaaactaag tacagactat ttcactgtaa agcagagaag 9000
ttcttttgaa ggagaatctc cagtgaagaa agagttcttc acttttactt ccatttcctc 9060
ttgtgggtga ccctcaatgc tccttgtaaa actccaatat tttaaacatg gctgttttgc 9120
ctttctttgc ttctttttag catgaatgag acagatgata ctttaaaaaa gtaattaaaa 9180
aaaaaaactt gtgaaaatac atggccataa tacagaaccc aatacaatga tctcctttac 9240
caaattgtta tgtttgtact tttgtagata gctttccaat tcagagacag ttattctgtg 9300
taaaggtctg acttaacaag aaaagatttc cctttaccca aagaatccca gtccttattt 9360
gctggtcaat aagcagggtc cccaggaatg gggtaacttt cagcaccctc taacccacta 9420
gttattagta gactaattaa gtaaacttat cgcaagttga ggaaacttag aaccaactaa 9480
aattctgctt ttactgggat tttgtttttt caaaccagaa acctttactt aagttgacta 9540
ctattaatga attttggtct ctcttttaag tgctcttctt aaaaatgtta tcttactgct 9600
gagaagttca agtttgggaa gtacaaggag gaatagaaac ttaagagatt ttcttttaga 9660
gcctcttctg tatttagccc tgtaggattt tttttttttt tttttttttt ggtgttgttg 9720
agcttcagtg aggctattca ttcacttata ctgataatgt ctgagatact gtgaatgaaa 9780
tactatgtat gcttaaacct aagaggaaat attttcccaa aattattctt cccgaaaagg 9840
aggagttgcc ttttgattga gttcttgcaa atctcacaac gactttattt tgaacaatac 9900
tgtttgggga tgatgcatta gtttgaaaca acttcagttg tagctgtcat ctgataaaat 9960
tgcttcacag ggaaggaaat ttaacacgga tctagtcatt attcttgtta gattgaatgt 10020
gtgaattgta attgtaaaca ggcatgataa ttattacttt aaaaactaaa aacagtgaat 10080
agttagttgt ggaggttact aaaggatggt ttttttttaa ataaaacttt cagcattatg 10140
caaatgggca tatggcttag gataaaactt ccagaagtag catcacattt aaattctcaa 10200
gcaacttaat aatatggggc tctgaaaaac tggttaaggt tactccaaaa atggccctgg 10260
gtctgacaaa gattctaact taaagatgct tatgaagact ttgagtaaaa tcatttcata 10320
aaataagtga ggaaaaacaa ctagtattaa attcatctta aataatgtat gatttaaaaa 10380
atatgtttag ctaaaaatgc atagtcattt gacaatttca tttatatctc aaaaaattta 10440
cttaaccaag ttggtcacaa aactgatgag actggtggtg gtagtgaata aatgagggac 10500
catccatatt tgagacactt tacatttgtg atgtgttata ctgaattttc agtttgattc 10560
tatagactac aaatttcaaa attacaattt caagatgtaa taagtagtaa tatcttgaaa 10620
tagctctaaa gggaattttt ctgttttatt gattcttaaa atatatgtgc tgattttgat 10680
ttgcatttgg gtagattata cttttatgag tatggaggtt aggtattgat tcaagttttc 10740
cttacctatt tggtaaggat ttcaaagtct ttttgtgctt ggttttcctc atttttaaat 10800
atgaaatata ttgatgacct ttaacaaatt ttttttatct caaattttaa aggagatctt 10860
ttctaaaaga ggcatgatga cttaatcatt gcatgtaaca gtaaacgata aaccaatgat 10920
tccatactct ctaaagaata aaagtgagct ttagggccgg gcatggtcag aaatttgaca 10980
ccaacctggc caacatggcg aaaccccgtc tctactaaaa atacaaaaat cagccgggca 11040
tggtggcggc acctatagtc ccagctactt gggaggatga gacaggagag tcacttgaac 11100
ctgggaggag aggttgcagt gagctgagat cacgccattg cactccagcc tgagcaatga 11160
aagcaaaact ccatctcaaa aaaaaaaaaa gaaaagaaag aataaaagtg agctttggat 11220
tgcatataaa tcctttagac atgtagtaga cttgtttgat actgtgtttg aacaaattac 11280
gaagtatttt catcaaagaa tgttattgtt tgatgttatt tttatttttt attgcccagc 11340
ttctctcata ttacgtgatt ttcttcactt catgtcactt tattgtgcag ggtcagagta 11400
ttattccaat gcttactgga gaagtgattc ctgtaatgga actgctttca tctatgaaat 11460
cacacagtgt tcctgaagaa atagatgtaa gtttaaatga gagcaattat acactttatg 11520
agttttttgg ggttatagta ttattatgta tattattaat attctaattt taatagtaag 11580
gactttgtca tacatactat tcacatacag tattagccac tttagcaaat aagcacacac 11640
aaaatcctgg attttatggc aaaacagagg catttttgat cagtgatgac aaaattaaat 11700
tcattttgtt tatttcatta cttttataat tcctaaaagt gggaggatcc cagctcttat 11760
aggagcaatt aatatttaat gtagtgtctt ttgaaacaaa actgtgtgcc aaagtagtaa 11820
ccattaatgg aagtttactt gtagtcacaa atttagtttc cttaatcatt tgttgaggac 11880
gttttgaatc acacactatg agtgttaaga gataccttta ggaaactatt cttgttgttt 11940
tctgattttg tcatttaggt tagtctcctg attctgacag ctcagaagag gaagttgttc 12000
ttgtaaaaat tgtttaacct gcttgaccag ctttcacatt tgttcttctg aagtttatgg 12060
tagtgcacag agattgtttt ttggggagtc ttgattctcg gaaatgaagg cagtgtgtta 12120
tattgaatcc agacttccga aaacttgtat attaaaagtg ttatttcaac actatgttac 12180
agccagacta atttttttat tttttgatgc attttagata gctgatacag tactcaatga 12240
tgatgatatt ggtgacagct gtcatgaagg ctttcttctc aagtaagaat ttttcttttc 12300
ataaaagctg gatgaagcag ataccatctt atgctcacct atgacaagat ttggaagaaa 12360
gaaaataaca gactgtctac ttagattgtt ctagggacat tacgtatttg aactgttgct 12420
taaatttgtg ttatttttca ctcattatat ttctatatat atttggtgtt attccatttg 12480
ctatttaaag aaaccgagtt tccatcccag acaagaaatc atggcccctt gcttgattct 12540
ggtttcttgt tttacttctc attaaagcta acagaatcct ttcatattaa gttgtactgt 12600
agatgaactt aagttattta ggcgtagaac aaaattattc atatttatac tgatcttttt 12660
ccatccagca gtggagttta gtacttaaga gtttgtgccc ttaaaccaga ctccctggat 12720
taatgctgtg tacccgtggg caaggtgcct gaattctcta tacacctatt tcctcatctg 12780
taaaatggca ataatagtaa tagtacctaa tgtgtagggt tgttataagc attgagtaag 12840
ataaataata taaagcactt agaacagtgc ctggaacata aaaacactta ataatagctc 12900
atagctaaca tttcctattt acatttcttc tagaaatagc cagtatttgt tgagtgccta 12960
catgttagtt cctttactag ttgctttaca tgtattatct tatattctgt tttaaagttt 13020
cttcacagtt acagattttc atgaaatttt acttttaata aaagagaagt aaaagtataa 13080
agtattcact tttatgttca cagtcttttc ctttaggctc atgatggagt atcagaggca 13140
tgagtgtgtt taacctaaga gccttaatgg cttgaatcag aagcacttta gtcctgtatc 13200
tgttcagtgt cagcctttca tacatcattt taaatcccat ttgactttaa gtaagtcact 13260
taatctctct acatgtcaat ttcttcagct ataaaatgat ggtatttcaa taaataaata 13320
cattaattaa atgatattat actgactaat tgggctgttt taaggctcaa taagaaaatt 13380
tctgtgaaag gtctctagaa aatgtaggtt cctatacaaa taaaagataa cattgtgctt 13440
atagcttcgg tgtttatcat ataaagctat tctgagttat ttgaagagct cacctacttt 13500
tttttgtttt tagtttgtta aattgtttta taggcaatgt ttttaatctg ttttctttaa 13560
cttacagtgc catcagctca cacttgcaaa cctgtggctg ttccgttgta gtaggtagca 13620
gtgcagagaa agtaaataag gtagtttatt ttataatcta gcaaatgatt tgactcttta 13680
agactgatga tatatcatgg attgtcattt aaatggtagg ttgcaattaa aatgatctag 13740
tagtataagg aggcaatgta atctcatcaa attgctaaga caccttgtgg caacagtgag 13800
tttgaaataa actgagtaag aatcatttat cagtttattt tgatagctcg gaaataccag 13860
tgtcagtagt gtataaatgg ttttgagaat atattaaaat cagatatata aaaaaaatta 13920
ctcttctatt tcccaatgtt atctttaaca aatctgaaga tagtcatgta cttttggtag 13980
tagttccaaa gaaatgttat ttgtttattc atcttgattt cattgtcttc gctttccttc 14040
taaatctgtc ccttctaggg agctattggg attaagtggt cattgattat tatactttat 14100
tcagtaatgt ttctgaccct ttccttcagt gctacttgag ttaattaagg attaatgaac 14160
agttacattt ccaagcatta gctaataaac taaaggattt tgcacttttc ttcactgacc 14220
attagttaga aagagttcag agataagtat gtgtatcttt caatttcagc aaacctaatt 14280
ttttaaaaaa agttttacat aggaaatatg ttggaaatga tactttacaa agatattcat 14340
aatttttttt tgtaatcagc tactttgtat atttacatga gccttaattt atatttctca 14400
tataaccatt tatgagagct tagtatacct gtgtcattat attgcatcta cgaactagtg 14460
accttattcc ttctgttacc tcaaacaggt ggctttccat ctgtgatctc caaagcctta 14520
ggttgcacag agtgactgcc gagctgcttt atgaagggag aaaggctcca tagttggagt 14580
gttttttttt ttttttttaa acatttttcc catcctccat cctcttgagg gagaatagct 14640
taccttttat cttgttttaa tttgagaaag aagttgccac cactctaggt tgaaaaccac 14700
tcctttaaca taataactgt ggatatggtt tgaatttcaa gatagttaca tgccttttta 14760
tttttcctaa tagagctgta ggtcaaatat tattagaatc agatttctaa atcccaccca 14820
atgacctgct tattttaaat caaattcaat aattaattct cttctttttg gaggatctgg 14880
acattctttg atatttctta caacgaattt catgtgtaga cccactaaac agaagctata 14940
aaagttgcat ggtcaaataa gtctgagaaa gtctgcagat gatataattc acctgaagag 15000
tcacagtatg tagccaaatg ttaaaggttt tgagatgcca tacagtaaat ttaccaagca 15060
ttttctaaat ttatttgacc acagaatccc tattttaagc aacaactgtt acatcccatg 15120
gattccaggt gactaaagaa tacttatttc ttaggatatg ttttattgat aataacaatt 15180
aaaatttcag atatctttca taagcaaatc agtggtcttt ttacttcatg ttttaatgct 15240
aaaatatttt cttttataga tagtcagaac attatgcctt tttctgactc cagcagagag 15300
aaaatgctcc aggttatgtg aagcagaatc atcatttaaa tatgagtcag ggctctttgt 15360
acaaggcctg ctaaaggtat agtttctagt tatcacaagt gaaaccactt ttctaaaatc 15420
atttttgaga ctctttatag acaaatctta aatattagca tttaatgtat ctcatattga 15480
catgcccaga gactgacttc ctttacacag ttctgcacat agactatatg tcttatggat 15540
ttatagttag tatcatcagt gaaacaccat agaataccct ttgtgttcca ggtgggtccc 15600
tgttcctaca tgtctagcct caggactttt ttttttttaa cacatgctta aatcaggttg 15660
cacatcaaaa ataagatcat ttctttttaa ctaaatagat ttgaatttta ttgaaaaaaa 15720
attttaaaca tctttaagaa gcttatagga tttaagcaat tcctatgtat gtgtactaaa 15780
atatatatat ttctatatat aatatatatt agaaaaaaat tgtatttttc ttttatttga 15840
gtctactgtc aaggagcaaa acagagaaat gtaaattagc aattatttat aatacttaaa 15900
gggaagaaag ttgttcacct tgttgaatct attattgtta tttcaattat agtcccaaga 15960
cgtgaagaaa tagctttcct aatggttatg tgattgtctc atagtgacta ctttcttgag 16020
gatgtagcca cggcaaaatg aaataaaaaa atttaaaaat tgttgcaaat acaagttata 16080
ttaggctttt gtgcattttc aataatgtgc tgctatgaac tcagaatgat agtatttaaa 16140
tatagaaact agttaaagga aacgtagttt ctatttgagt tatacatatc tgtaaattag 16200
aacttctcct gttaaaggca taataaagtg cttaatactt ttgtttcctc agcaccctct 16260
catttaatta tataatttta gttctgaaag ggacctatac cagatgccta gaggaaattt 16320
caaaactatg atctaatgaa aaaatattta atagttctcc atgcaaatac aaatcatata 16380
gttttccaga aaataccttt gacattatac aaagatgatt atcacagcat tataatagta 16440
aaaaaatgga aatagcctct ttcttctgtt ctgttcatag cacagtgcct catacgcagt 16500
aggttattat tacatggtaa ctggctaccc caactgatta ggaaagaagt aaatttgttt 16560
tataaaaata catactcatt gaggtgcata gaataattaa gaaattaaaa gacacttgta 16620
attttgaatc cagtgaatac ccactgttaa tatttggtat atctctttct agtctttttt 16680
tcccttttgc atgtattttc tttaagactc ccacccccac tggatcatct ctgcatgttc 16740
taatctgctt ttttcacagc agattctaag cctctttgaa tatcaacaca aacttcaaca 16800
acttcatcta tagatgccaa ataataaatt catttttatt tacttaacca cttcctttgg 16860
atgcttaggt cattctgatg ttttgctatt gaaaccaatg ctatactgaa cacttctgtc 16920
actaaaactt tgcacacact catgaatagc ttcttaggat aaatttttag agatggattt 16980
gctaaatcag agaccatttt ttaaaattaa aaaacaatta ttcatatcgt ttggcatgta 17040
agacagtaaa ttttcctttt attttgacag gattcaactg gaagctttgt gctgcctttc 17100
cggcaagtca tgtatgctcc atatcccacc acacacatag atgtggatgt caatactgtg 17160
aagcagatgc caccctgtca tgaacatatt tataatcagc gtagatacat gagatccgag 17220
ctgacagcct tctggagagc cacttcagaa gaagacatgg ctcaggatac gatcatctac 17280
actgacgaaa gctttactcc tgatttgtac gtaatgctct gcctgctggt actgtagtca 17340
agcaatatga aattgtgtct tttacgaata aaaacaaaac agaagttgca tttaaaaaga 17400
aagaaatatt accagcagaa ttatgcttga agaaacattt aatcaagcat ttttttctta 17460
aatgttcttc tttttccata caattgtgtt taccctaaaa taggtaagat taacccttaa 17520
agtaaatatt taactatttg tttaataaat atatattgag ctcctaggca ctgttctagg 17580
taccgggctt aatagtggcc aaccagacag ccccagcccc agcccctaca ttgtgtatag 17640
tctattatgt aacagttatt gaatggactt attaacaaaa ccaaagaagt aattctaagt 17700
cttttttttc ttgacatatg aatataaaat acagcaaaac tgttaaaata tattaatgga 17760
acattttttt actttgcatt ttatattgtt attcacttct tatttttttt taaaaaaaaa 17820
agcctgaaca gtaaattcaa aaggaaaagt aatgataatt aattgttgag catggaccca 17880
acttgaaaaa aaaaatgatg atgataaatc tataatccta aaaccctaag taaacactta 17940
aaagatgttc tgaaatcagg aaaagaatta tagtatactt ttgtgtttct cttttatcag 18000
ttgaaaaaag gcacagtagc tcatgcctgt aagaacagag ctttgggagt gcaaggcagg 18060
cggatcactt gaggccagga gttccagacc agcctgggca acatagtgaa accccatctc 18120
tacaaaaaat aaaaaagaat tattggaatg tgtttctgtg tgcctgtaat cctagctatt 18180
ccgaaagctg aggcaggagg atcttttgag cccaggagtt tgaggttaca gggagttatg 18240
atgtgccagt gtactccagc ctggggaaca ccgagactct gtcttattta aaaaaaaaaa 18300
aaaaaaaatg cttgcaataa tgcctggcac atagaaggta acagtaagtg ttaactgtaa 18360
taacccaggt ctaagtgtgt aaggcaatag aaaaattggg gcaaataagc ctgacctatg 18420
tatctacaga atcagtttga gcttaggtaa cagacctgtg gagcaccagt aattacacag 18480
taagtgttaa ccaaaagcat agaataggaa tatcttgttc aagggacccc cagccttata 18540
catctcaagg tgcagaaaga tgacttaata taggacccat tttttcctag ttctccagag 18600
tttttattgg ttcttgagaa agtagtaggg gaatgtttta gaaaatgaat tggtccaact 18660
gaaattacat gtcagtaagt ttttatatat tggtaaattt tagtagacat gtagaagttt 18720
tctaattaat ctgtgccttg aaacattttc ttttttccta aagtgcttag tattttttcc 18780
gttttttgat tggttacttg ggagcttttt tgaggaaatt tagtgaactg cagaatgggt 18840
ttgcaaccat ttggtatttt tgttttgttt tttagaggat gtatgtgtat tttaacattt 18900
cttaatcatt tttagccagc tatgtttgtt ttgctgattt gacaaactac agttagacag 18960
ctattctcat tttgctgatc atgacaaaat aatatcctga atttttaaat tttgcatcca 19020
gctctaaatt ttctaaacat aaaattgtcc aaaaaatagt attttcagcc actagattgt 19080
gtgttaagtc tattgtcaca gagtcatttt acttttaagt atatgttttt acatgttaat 19140
tatgtttgtt atttttaatt ttaacttttt aaaataattc cagtcactgc caatacatga 19200
aaaattggtc actggaattt tttttttgac ttttatttta ggttcatgtg tacatgtgca 19260
ggtgtgttat acaggtaaat tgcgtgtcat gagggtttgg tgtacaggtg atttcattac 19320
ccaggtaata agcatagtac ccaataggta gttttttgat cctcaccctt ctcccaccct 19380
caagtaggcc ctggtgttgc tgtttccttc tttgtgtcca tgtatactca gtgtttagct 19440
cccacttaga agtgagaaca tgcggtagtt ggttttctgt tcctggatta gttcacttag 19500
gataatgacc tctagctcca tctggttttt atggctgcat agtattccat ggtgtatatg 19560
tatcacattt tctttatcca gtctaccatt gataggcatt taggttgatt ccctgtcttt 19620
gttatcatga atagtgctgt gatgaacata cacatgcatg tgtctttatg gtagaaaaat 19680
ttgtattcct ttaggtacat atagaataat ggggttgcta gggtgaatgg tagttctatt 19740
ttcagttatt tgagaaatct tcaaactgct tttcataata gctaaactaa tttacagtcc 19800
cgccagcagt gtataagtgt tcccttttct ccacaacctt gccaacatct gtgatttttt 19860
gactttttaa taatagccat tcctagagaa ttgatttgca attctctatt agtgatatta 19920
agcatttttt catatgcttt ttagctgtct gtatatattc ttctgaaaaa ttttcatgtc 19980
ctttgcccag tttgtagtgg ggtgggttgt tttttgcttg ttaattagtt ttaagttcct 20040
tccagattct gcatatccct ttgttggata catggtttgc agatattttt ctcccattgt 20100
gtaggttgtc ttttactctg ttgatagttt cttttgccat gcaggagctc gttaggtccc 20160
atttgtgttt gtttttgttg cagttgcttt tggcgtcttc atcataaaat ctgtgccagg 20220
gcctatgtcc agaatggtat ttcctaggtt gtcttccagg gtttttacaa ttttagattt 20280
tacgtttatg tctttaatcc atcttgagtt gatttttgta tatggcacaa ggaaggggtc 20340
cagtttcact ccaattccta tggctagcaa ttatcccagc accatttatt gaatacggag 20400
tcctttcccc attgcttgtt ttttgtcaac tttgttgaag atcagatggt tgtaagtgtg 20460
tggctttatt tcttggctct ctattctcca ttggtctatg tgtctgtttt tataacagta 20520
ccctgctgtt caggttccta tagcctttta gtataaaatc ggctaatgtg atgcctccag 20580
ctttgttctt tttgcttagg attgctttgg ctatttgggc tcctttttgg gtccatatta 20640
attttaaaac agttttttct ggttttgtga aggatatcat tggtagttta taggaatagc 20700
attgaatctg tagattgctt tgggcagtat ggccatttta acaatattaa ttcttcctat 20760
ctatgaatat ggaatgtttt tccatgtgtt tgtgtcatct ctttatacct gatgtataaa 20820
gaaaagctgg tattattcct actcaatctg ttccaaaaaa ttgaggagga ggaactcttc 20880
cctaatgagg ccagcatcat tctgatacca aaacctggca gagacacaac agaaaaaaga 20940
aaacttcagg ccaatatcct tgatgaatat agatgcaaaa atcctcaaca aaatactagc 21000
aaaccaaatc cagcagcaca tcaaaaagct gatctacttt gatcaagtag gctttatccc 21060
tgggatgcaa ggttggttca acatacacaa atcaataagt gtgattcatc acataaacag 21120
agctaaaaac aaaaaccaca agattatctc aataggtaga gaaaaggttg tcaataaaat 21180
ttaacatcct ccatgttaaa aaccttcagt aggtcaggtg tagtgactca cacctgtaat 21240
cccagcactt tgggaggcca aggcgggcat atctcttaag cccaggagtt caagacgagc 21300
ctaggcagca tggtgaaacc ccatctctac aaaaaaaaaa aaaaaaaaaa attagcttgg 21360
tatggtgaca tgcacctata gtcccagcta ttcaggaggt tgaggtggga ggattgtttg 21420
agcccgggag gcagaggttg gcagcgagct gagatcatgc caccgcactc cagcctgggc 21480
aacggagtga gaccctgtct caaaaaagaa aaatcacaaa caatcctaaa caaactaggc 21540
attgaaggaa catgcctcaa aaaaataaga accatctatg acagacccat agccaatatc 21600
ttaccaaatg ggcaaaagct ggaagtattc tccttgagaa ccgtaacaag acaaggatgt 21660
ccactctcac cactcctttt cagcatagtt ctggaagtcc tagccagagc aatcaggaaa 21720
gagaaagaaa gaaagacatt cagataggaa gagaagaagt caaactattt ctgtttgcag 21780
gcagtataat tctgtaccta gaaaatctca tagtctctgc ccagaaactc ctaaatctgt 21840
taaaaatttc agcaaagttt tggcattctc tatactccaa caccttccaa agtgagagca 21900
aaatcaagaa cacagtccca ttcacaatag ccgcaaaacg aataaaatac ctaggaatcc 21960
agctaaccag ggaggtgaaa gatctctatg agaattacaa aacactgctg aaagaaatca 22020
gagatgacac aaacaaatgg aaatgttctt ttttaacacc ttgctttatc taattcactt 22080
atgatgaaga tactcattca gtggaacagg tataataagt ccactcgatt aaatataagc 22140
cttattctct ttccagagcc caagaagggg cactatcagt gcccagtcaa taatgacgaa 22200
atgctaatat ttttcccctt tacggtttct ttcttctgta gtgtggtaca ctcgtttctt 22260
aagataagga aacttgaact accttcctgt ttgcttctac acatacccat tctctttttt 22320
tgccactctg gtcaggtata ggatgatccc taccactttc agttaaaaac tcctcctctt 22380
actaaatgtt ctcttaccct ctggcctgag tagaacctag ggaaaatgga agagaaaaag 22440
atgaaaggga ggtggggcct gggaagggaa taagtagtcc tgtttgtttg tgtgtttgct 22500
ttagcacctg ctatatccta ggtgctgtgt taggcacaca ttattttaag tggccattat 22560
attactacta ctcactctgg tcgttgccaa ggtaggtagt actttcttgg atagttggtt 22620
catgttactt acagatggtg ggcttgttga ggcaaaccca gtggataatc atcggagtgt 22680
gttctctaat ctcactcaaa tttttcttca cattttttgg tttgttttgg tttttgatgg 22740
tagtggctta tttttgttgc tggtttgttt tttgtttttt tttgagatgg caagaattgg 22800
tagttttatt tattaattgc ctaagggtct ctactttttt taaaagatga gagtagtaaa 22860
atagattgat agatacatac atacccttac tggggactgc ttatattctt tagagaaaaa 22920
attacatatt agcctgacaa acaccagtaa aatgtaaata tatccttgag taaataaatg 22980
aatgtatatt ttgtgtctcc aaatatatat atctatattc ttacaaatgt gtttatatgt 23040
aatatcaatt tataagaact taaaatgttg gctcaagtga gggattgtgg aaggtagcat 23100
tatatggcca tttcaacatt tgaacttttt tcttttcttc attttcttct tttcttcagg 23160
aatatttttc aagatgtctt acacagagac actctagtga aagccttcct ggatcaggta 23220
aatgttgaac ttgagattgt cagagtgaat gatatgacat gttttctttt ttaatatatc 23280
ctacaatgcc tgttctatat atttatattc ccctggatca tgccccagag ttctgctcag 23340
caattgcagt taagttagtt acactacagt tctcagaaga gtctgtgagg gcatgtcaag 23400
tgcatcatta cattggttgc ctcttgtcct agatttatgc ttcgggaatt cagacctttg 23460
tttacaatat aataaatatt attgctatct tttaaagata taataataag atataaagtt 23520
gaccacaact actgtttttt gaaacataga attcctggtt tacatgtatc aaagtgaaat 23580
ctgacttagc ttttacagat ataatatata catatatata tcctgcaatg cttgtactat 23640
atatgtagta caagtatata tatatgtttg tgtgtgtata tatatatagt acgagcatat 23700
atacatatta ccagcattgt aggatatata tatgtttata tattaaaaaa aagttataaa 23760
cttaaaaccc tattatgtta tgtagagtat atgttatata tgatatgtaa aatatataac 23820
atatactcta tgatagagtg taatatattt tttatatata ttttaacatt tataaaatga 23880
tagaattaag aattgagtcc taatctgttt tattaggtgc tttttgtagt gtctggtctt 23940
tctaaagtgt ctaaatgatt tttccttttg acttattaat ggggaagagc ctgtatatta 24000
acaattaaga gtgcagcatt ccatacgtca aacaacaaac attttaattc aagcattaac 24060
ctataacaag taagtttttt tttttttttt gagaaaggga ggttgtttat ttgcctgaaa 24120
tgactcaaaa atatttttga aacatagtgt acttatttaa ataacatctt tattgtttca 24180
ttcttttaaa aaatatctac ttaattacac agttgaagga aatcgtagat tatatggaac 24240
ttatttctta atatattaca gtttgttata ataacattct ggggatcagg ccaggaaact 24300
gtgtcataga taaagctttg aaataatgag atccttatgt ttactagaaa ttttggattg 24360
agatctatga ggtctgtgac atattgcgaa gttcaaggaa aattcgtagg cctggaattt 24420
catgcttctc aagctgacat aaaatccctc ccactctcca cctcatcata tgcacacatt 24480
ctactcctac ccacccactc caccccctgc aaaagtacag gtatatgaat gtctcaaaac 24540
cataggctca tcttctagga gcttcaatgt tatttgaaga tttgggcaga aaaaattaag 24600
taatacgaaa taacttatgt atgagtttta aaagtgaagt aaacatggat gtattctgaa 24660
gtagaatgca aaatttgaat gcatttttaa agataaatta gaaaacttct aaaaactgtc 24720
agattgtctg ggcctggtgg cttatgcctg taatcccagc actttgggag tccgaggtgg 24780
gtggatcaca aggtcaggag atcgagacca tcctgccaac atggtgaaac cccgtctcta 24840
ctaagtatac aaaaattagc tgggcgtggc agcgtgtgcc tgtaatccca gctacctggg 24900
aggctgaggc aggagaatcg cttgaaccca ggaggtgtag gttgcagtga gtcaagatcg 24960
cgccactgca ctttagcctg gtgacagagc tagactccgt ctcaaaaaaa aaaaaaaata 25020
tcagattgtt cctacaccta gtgcttctat accacactcc tgttaggggg catcagtgga 25080
aatggttaag gagatgttta gtgtgtattg tctgccaagc actgtcaaca ctgtcataga 25140
aacttctgta cgagtagaat gtgagcaaat tatgtgttga aatggttcct ctccctgcag 25200
gtctttcagc tgaaacctgg cttatctctc agaagtactt tccttgcaca gtttctactt 25260
gtccttcaca gaaaagcctt gacactaata aaatatatag aagacgatac gtgagtaaaa 25320
ctcctacacg gaagaaaaac ctttgtacat tgtttttttg ttttgtttcc tttgtacatt 25380
ttctatatca taatttttgc gcttcttttt tttttttttt tttttttttt tccattattt 25440
ttaggcagaa gggaaaaaag ccctttaaat ctcttcggaa cctgaagata gaccttgatt 25500
taacagcaga gggcgatctt aacataataa tggctctggc tgagaaaatt aaaccaggcc 25560
tacactcttt tatctttgga agacctttct acactagtgt gcaagaacga gatgttctaa 25620
tgacttttta aatgtgtaac ttaataagcc tattccatca caatcatgat cgctggtaaa 25680
gtagctcagt ggtgtgggga aacgttcccc tggatcatac tccagaattc tgctctcagc 25740
aattgcagtt aagtaagtta cactacagtt ctcacaagag cctgtgaggg gatgtcaggt 25800
gcatcattac attgggtgtc tcttttccta gatttatgct tttgggatac agacctatgt 25860
ttacaatata ataaatatta ttgctatctt ttaaagatat aataatagga tgtaaacttg 25920
accacaacta ctgttttttt gaaatacatg attcatggtt tacatgtgtc aaggtgaaat 25980
ctgagttggc ttttacagat agttgacttt ctatcttttg gcattctttg gtgtgtagaa 26040
ttactgtaat acttctgcaa tcaactgaaa actagagcct ttaaatgatt tcaattccac 26100
agaaagaaag tgagcttgaa cataggatga gctttagaaa gaaaattgat caagcagatg 26160
tttaattgga attgattatt agatcctact ttgtggattt agtccctggg attcagtctg 26220
tagaaatgtc taatagttct ctatagtcct tgttcctggt gaaccacagt tagggtgttt 26280
tgtttatttt attgttcttg ctattgttga tattctatgt agttgagctc tgtaaaagga 26340
aattgtattt tatgttttag taattgttgc caacttttta aattaatttt cattattttt 26400
gagccaaatt gaaatgtgca cctcctgtgc cttttttctc cttagaaaat ctaattactt 26460
ggaacaagtt cagatttcac tggtcagtca ttttcatctt gttttcttct tgctaagtct 26520
taccatgtac ctgctttggc aatcattgca actctgagat tataaaatgc cttagagaat 26580
atactaacta ataagatctt tttttcagaa acagaaaata gttccttgag tacttccttc 26640
ttgcatttct gcctatgttt ttgaagttgt tgctgtttgc ctgcaatagg ctataaggaa 26700
tagcaggaga aattttactg aagtgctgtt ttcctaggtg ctactttggc agagctaagt 26760
tatcttttgt tttcttaatg cgtttggacc attttgctgg ctataaaata actgattaat 26820
ataattctaa cacaatgttg acattgtagt tacacaaaca caaataaata ttttatttaa 26880
aattctggaa gtaatataaa agggaaaata tatttataag aaagggataa aggtaataga 26940
gcccttctgc cccccaccca ccaaatttac acaacaaaat gacatgttcg aatgtgaaag 27000
gtcataatag ctttcccatc atgaatcaga aagatgtgga cagcttgatg ttttagacaa 27060
ccactgaact agatgactgt tgtactgtag ctcagtcatt taaaaaatat ataaatacta 27120
ccttgtagtg tcccatactg tgttttttac atggtagatt cttatttaag tgctaactgg 27180
ttattttctt tggctggttt attgtactgt tatacagaat gtaagttgta cagtgaaata 27240
agttattaaa gcatgtgtaa acattgttat atatcttttc tcctaaatgg agaattttga 27300
ataaaatata tttgaaattt t 27321

Claims (28)

1. A method of integrating a transgene into an endogenous gene, the method comprising:
a. administering a transgene, wherein the transgene comprises
i. A first splice donor sequence and a second splice donor sequence,
A first partial coding sequence and a second partial coding sequence, and
a bidirectional promoter or a first promoter and a second promoter;
administering at least one rare-cutting endonuclease targeted to a site within the endogenous gene,
wherein the transgene is integrated within the endogenous gene.
2. The method of claim 1, wherein said first splice donor is operably linked to said first portion of coding sequence and said second splice donor is operably linked to said second portion of coding sequence.
3. The method of claim 2, wherein the first partial coding sequence is operably linked to the first promoter and the second partial coding sequence is operably linked to the second promoter.
4. The method of claim 2, wherein said first partial coding sequence and said second partial coding sequence are operably linked to a bidirectional promoter.
5. The method of claim 3, wherein said first and second splice donors, said first and second partial coding sequences, and said first and second promoters are oriented in a head-to-head orientation.
6. The method of claim 5, wherein the transgene further comprises a first target site and a second target site for one or more rare-cutting endonucleases, wherein the target sites are flanking the first splice donor and the second splice donor.
7. The method of claim 5, wherein the transgene further comprises first and second homology arms flanking the first and second splice donors.
8. The method of claim 5, wherein the transgene is carried within an adeno-associated viral vector.
9. The method of claim 7, wherein the transgene further comprises a first target site and a second target site for the one or more rare-cutting endonucleases, wherein the target sites are flanking the first splice donor and the second splice donor.
10. The method of claim 9, wherein the first and second target sites are flanking the first and second homology arms.
11. The method of claim 1, wherein the transgene is integrated within an intron or at an exon-intron junction of the endogenous gene.
12. The method of claim 1, wherein the transgene is integrated within an intron or at an exon-intron junction of the ATXN2 gene or SNCA gene.
13. The method of claim 12, wherein the transgene comprises a first and second partial coding sequence encoding a peptide produced by exon 1 of the non-pathogenic ATXN2 gene.
14. The method of claim 12, wherein the transgene comprises a first portion of coding sequence and a second portion of coding sequence encoding a peptide produced by exon 2 of a non-pathogenic SNCA gene.
15. The method of claim 1, wherein the nuclease is a CRISPR/Cas12a nuclease or a CRISPR/Cas9 nuclease.
16. The method according to claim 1, wherein the first partial coding sequence and the second partial coding sequence encode the same amino acid.
17. The method of claim 1, wherein the first coding sequence and the second coding sequence differ in nucleic acid sequence but encode the same amino acid.
18. The method of claim 1, wherein the transgene is carried on a vector, wherein the vector is in a form selected from the group consisting of double-stranded linear DNA, double-stranded circular DNA, and a viral vector.
19. The method of claim 18, wherein the viral vector is selected from an adenoviral vector, an adeno-associated viral vector, or a lentiviral vector.
20. The method of claim 19, wherein the transgene is equal to or less than 4.7 kb.
21. The method of claim 1, wherein the endogenous gene is a wild-type gene for the partial coding sequence.
22. The method of claim 21, wherein the endogenous gene is abnormal or pathogenic and the partial coding sequence encodes a partial protein produced from a functional version of the endogenous gene.
23. The method of claim 22, wherein the first and second partial coding sequences differ in nucleic acid sequence as compared to the corresponding endogenous gene.
24. The method of claim 1, wherein the endogenous gene is selected from SOD1, TRPV4, CHRNA1, CHRND, CHRNE, CHRNB1, PRPS1, LRRK2, STIM1, FGFR3, MECP2, SNCA, ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7, TBP, HTT, AR, FXN, DMPK, PABPN1, ATXN8, RHO, or C9orf 72.
25. The method of claim 1, wherein the transgene further comprises a first terminator and a second terminator.
26. A method of integrating a transgene into an endogenous gene, the method comprising:
a. administering a transgene, wherein the transgene comprises
i. A splicing donor sequence,
A partial coding sequence,
iii a promoter,
An RNA interference cassette, and
v. optionally a first and second homology arm or a left transposon end and a right transposon end;
b. administering at least one rare-cutting endonuclease or transposase that targets a site within the endogenous gene,
wherein the transgene is integrated within the endogenous gene.
27. A method of integrating a transgene into an endogenous gene, the method comprising:
a. administering a transgene, wherein the transgene comprises
i. The tail end of the left rotating seat and the tail end of the right rotating seat,
A first splice donor sequence and a second splice donor sequence,
The first partial coding sequence and the second partial coding sequence,
A bidirectional promoter or a first promoter and a second promoter, and
v. optionally a first terminator and a second terminator;
b. the application of a transposase is carried out,
wherein the transgene is integrated within the endogenous gene.
28. A method of integrating a transgene into an endogenous gene, the method comprising:
a. administering a transgene, wherein the transgene comprises
i. A splice acceptor sequence,
A partial coding sequence,
iii a terminator,
An RNA interference cassette, and
v. optionally a first and second homology arm or a left transposon end and a right transposon end;
b. administering at least one rare-cutting endonuclease or transposase that targets a site within the endogenous gene,
wherein the transgene is integrated within the endogenous gene.
CN201980079896.8A 2018-11-01 2019-10-30 Methods for altering gene expression of genetic disorders Pending CN113166769A (en)

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US201862754548P 2018-11-01 2018-11-01
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US201862756175P 2018-11-06 2018-11-06
US62/756175 2018-11-06
US201962799615P 2019-01-31 2019-01-31
US62/799615 2019-01-31
PCT/US2019/058857 WO2020092557A2 (en) 2018-11-01 2019-10-30 Methods for altering gene expression for genetic disorders

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